Publications by authors named "Fabio Rinaldi"

80 Publications

Improving classification of low-resource COVID-19 literature by using Named Entity Recognition.

Genomics Inform 2021 Sep 30;19(3):e22. Epub 2021 Sep 30.

Dalle Molle Institute for Artificial Intelligence Research, IDSIA USI-SUPSI, Polo universitario Lugano-Campus Est, Via la Santa 1, CH-6962 Lugano, Switzerland.

Automatic document classification for highly interrelated classes is a demanding task that becomes more challenging when there is little labeled data for training. Such is the case of the coronavirus disease 2019 (COVID-19) Clinical repository-a repository of classified and translated academic articles related to COVID-19 and relevant to the clinical practice-where a 3-way classification scheme is being applied to COVID-19 literature. During the 7th Biomedical Linked Annotation Hackathon (BLAH7) hackathon, we performed experiments to explore the use of named-entity-recognition (NER) to improve the classification. We processed the literature with OntoGene's Biomedical Entity Recogniser (OGER) and used the resulting identified Named Entities (NE) and their links to major biological databases as extra input features for the classifier. We compared the results with a baseline model without the OGER extracted features. In these proof-of-concept experiments, we observed a clear gain on COVID-19 literature classification. In particular, NE's origin was useful to classify document types and NE's type for clinical specialties. Due to the limitations of the small dataset, we can only conclude that our results suggests that NER would benefit this classification task. In order to accurately estimate this benefit, further experiments with a larger dataset would be needed.
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http://dx.doi.org/10.5808/gi.21018DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8510872PMC
September 2021

Editor's introduction to the special section on the 7th Biomedical Linked Annotation Hackathon (BLAH7).

Genomics Inform 2021 Sep 30;19(3):e20. Epub 2021 Sep 30.

Center for Convergence Research of Advanced Technologies, Ewha Womans University, Seoul 03760, Korea.

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http://dx.doi.org/10.5808/gi.19.3.e1DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8510870PMC
September 2021

Protective effects of sunscreen (50+) and octatrienoic acid 0.1% in actinic keratosis and UV damages.

J Investig Med 2021 Sep 16. Epub 2021 Sep 16.

Human Microbiome Advanced Project, Milan, Italy.

Actinic keratosis is a form of dysplastic epidermal lesion resulting from chronic and excessive UV exposure with a certain risk of becoming cancerous. Current guidelines advocated the use of sunscreens to prevent photodamage. An efficient photoprotection must involve both primary protective factors such as UV filters and secondary factors (eg, antioxidants) able to disrupt the photochemical and genetic cascade triggered by UVs. An in vitro model of human skin (Phenion FT) was used to assess the photoprotective potential of a sunscreen containing inorganic sun-filters (50+ SPF) and 0.1% octatrienoic acid (KERA'+) after UVA (10 J/cm) and UVB (25 mJ/cm) by means of evaluation of the number of sunburn cells (SBCs) and apoptotic keratinocytes. Also resulting alterations in the gene expression of markers involved in apoptosis (Tumor protein 53), inflammation/immunosuppression (IL-6 and IL-8), oxidative stress (oxidative stress response enzyme heme oxygenase 1), remodeling (metalloproteinase 1) and cell-cell adhesion (E-cadherin) were investigated. Gene expression was investigated using quantitative real-time PCR. This work demonstrated that the sunscreen preparations under study (with and without 0.1% octatrienoic acid, respectively) can be distinguished about their ability to prevent UVs-induced damage. Synergism between the inorganic filters and 0.1% octatrienoic acid was found (KERA'+) on all end points analyzed and this effect was found to be statistically significant (p<0.05). Our data revealed that topical application of a sunscreen containing inorganic filters (50+SPF) and 0.1% octatrienoic acid can protect from SBC formation, reduce the number of apoptotic keratinocytes and protect from the main molecular alterations caused by UV radiations.
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http://dx.doi.org/10.1136/jim-2021-001972DOI Listing
September 2021

Enhancing Biomedical Relation Extraction with Transformer Models using Shortest Dependency Path Features and Triplet Information.

J Biomed Inform 2021 10 2;122:103893. Epub 2021 Sep 2.

Istituto Dalle Molle di Studi sull'Intelligenza Artificiale USI/SUPSI, Lugano, Switzerland; Department of Quantitative Biomedicine, University of Zurich, Zurich, Switzerland; Swiss Institute of Bioinformatics, Lausanne, Switzerland. Electronic address:

Entity relation extraction plays an important role in the biomedical, healthcare, and clinical research areas. Recently, pre-trained models based on transformer architectures and their variants have shown remarkable performances in various natural language processing tasks. Most of these variants were based on slight modifications in the architectural components, representation schemes and augmenting data using distant supervision methods. In distantly supervised methods, one of the main challenges is pruning out noisy samples. A similar situation can arise when the training samples are not directly available but need to be constructed from the given dataset. The BioCreative V Chemical Disease Relation (CDR) task provides a dataset that does not explicitly offer mention-level gold annotations and hence replicates the above scenario. Selecting the representative sentences from the given abstract or document text that could convey a potential entity relationship becomes essential. Most of the existing methods in literature propose to either consider the entire text or all the sentences which contain the entity mentions. This could be a computationally expensive and time consuming approach. This paper presents a novel approach to handle such scenarios, specifically in biomedical relation extraction. We propose utilizing the Shortest Dependency Path (SDP) features for constructing data samples by pruning out noisy information and selecting the most representative samples for model learning. We also utilize triplet information in model learning using the biomedical variant of BERT, viz., BioBERT. The problem is represented as a sentence pair classification task using the sentence and the entity-relation pair as input. We analyze the approach on both intra-sentential and inter-sentential relations in the CDR dataset. The proposed approach that utilizes the SDP and triplet features presents promising results, specifically on the inter-sentential relation extraction task. We make the code used for this work publicly available on Github..
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http://dx.doi.org/10.1016/j.jbi.2021.103893DOI Listing
October 2021

A Randomized Double-Blind Parallel-Group Study to Evaluate the Long-Term Effects of a Medical Device Containing 0.3% Octatrienoic Acid in the Treatment of Grade III Actinic Keratosis.

Dermatol Ther (Heidelb) 2021 Oct 2;11(5):1751-1762. Epub 2021 Sep 2.

Dermatology Unit, University of Campania Luigi Vanvitelli, Naples, Italy.

Introduction: Actinic keratosis (AK) consists of skin lesions with a milder degree of keratinocytic atypia. It can be also referred to as "field of cancerization," which can potentially evolve to cutaneous squamous cell carcinoma (SCC). Several therapeutic options are currently available, but not all are indicated on hyperkeratotic lesions. This study aimed to test the efficacy and tolerability of a medical device containing 2,4,6-octatrienoic acid and urea for the treatment of hyperkeratotic AK lesions.

Methods: Seventy male and female subjects with grade III AK were enrolled in this randomized double-blind parallel-group study. The product was applied once daily for three consecutive months. The primary efficacy endpoint was the reduction in the mean number of AK lesions per subject from baseline (T0) to the end of the trial (T1) and 3 months after the end of the treatment period (T2). Therefore, clearance of target AK lesions at the end of the treatment period and local skin reaction score (LSR) versus baseline were evaluated.

Results: There was a decrease of mean values from baseline to visit T2 in both treatment groups, but the decrease (versus baseline values) was more evident in the Kerà K2 group than in the placebo group (-42.78, SD 26.53, versus -6.20, SD 31.57), and the difference was statistically significant (p < 0.001). For 70 subjects (56.7%) in the Kerà K2 group and 3 (11.54%) in the placebo group, a significant (p < 0.005) partial clearance was evidenced. The product was well tolerated, and no serious adverse events were reported during the duration of the trial. Subject self-assessment of acceptability, local tolerability, and the cosmetic result was good at both T1 and T2 for both groups.

Conclusions: The medical device has demonstrated good efficacy in the reduction of visible AKs, encouraging its use.
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http://dx.doi.org/10.1007/s13555-021-00594-wDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8484398PMC
October 2021

Lisen&Curate: A platform to facilitate gathering textual evidence for curation of regulation of transcription initiation in bacteria.

Biochim Biophys Acta Gene Regul Mech 2021 Aug 28;1864(11-12):194753. Epub 2021 Aug 28.

Centro de Ciencias Genómicas, Universidad Nacional Autónoma de México, Avenida Universidad s/n Col. Chamilpa, 62210 Cuernavaca, Mor., Mexico; Department of Biomedical Engineering, Boston University, 44 Cummington Mall Room 403, 02215 Boston, MA, USA; Center for Genomic Regulation (CRG), Dr. Aiguader 88, 08003, Barcelona, Spain.

The number of published papers in biomedical research makes it rather impossible for a researcher to keep up to date. This is where manually curated databases contribute facilitating the access to knowledge. However, the structure required by databases strongly limits the type of valuable information that can be incorporated. Here, we present Lisen&Curate, a curation system that facilitates linking sentences or part of sentences (both considered sources) in articles with their corresponding curated objects, so that rich additional information of these objects is easily available to users. These sources are going to be offered both within RegulonDB and a new database, L-Regulon. To show the relevance of our work, two senior curators performed a curation of 31 articles on the regulation of transcription initiation of E. coli using Lisen&Curate. As a result, 194 objects were curated and 781 sources were recorded. We also found that these sources are useful to develop automatic approaches to detect objects in articles by observing word frequency patterns and by carrying out an open information extraction task. Sources may help to elaborate a controlled vocabulary of experimental methods. Finally, we discuss our ecosystem of interconnected applications, RegulonDB, L-Regulon, and Lisen&Curate, to facilitate the access to knowledge on regulation of transcription initiation in bacteria. We see our proposal as the starting point to change the way experimentalists connect a piece of knowledge with its evidence using RegulonDB.
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http://dx.doi.org/10.1016/j.bbagrm.2021.194753DOI Listing
August 2021

Real-time geospatial surveillance of localized emotional stress responses to COVID-19: A proof of concept analysis.

Health Place 2021 07 1;70:102598. Epub 2021 Jun 1.

University of Zurich, Department of Geography, Switzerland; University of Zurich, Epidemiology, Biostatistics and Prevention Institute, Switzerland.

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http://dx.doi.org/10.1016/j.healthplace.2021.102598DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8166515PMC
July 2021

In vitro and in vivo Evaluation on the Safety and Efficacy of a Brand-New Intracutaneous Filler with α1-R-Collagen.

Clin Cosmet Investig Dermatol 2021 12;14:501-512. Epub 2021 May 12.

Derming, Clinical Research, and Bioengineering Institute, Monza, Italy.

Nowadays, the most advanced skin anti-aging treatments are addressed to restore the extracellular matrix (ECM) homeostasis. ECM is considered the main player not only as physical support of the tegument but also at the biochemical level, thanks to its capacity to exchange nutrients, water, cellular mediators, and growth factors within and between cells. This study aimed to evaluate the in vitro and in vivo efficacy and aesthetic performance of a brand-new intracutaneous filler. The latter is based on novel concepts: besides filling it exerts a homeostatic balance of nutrients able to delay the skin aging process by sustaining physiological rejuvenation of the tissue and in the surrounding injection/implantation area. The brand-new intracutaneous filler was tested for in vitro capacity to stimulate extracellular matrix components production. Therefore, a single session for injection of the product under study was performed by a specialized dermatologist, using the bolus technique on the zygomatic protuberance of 20 healthy female subjects with midface volume loss, caused by aging. Results confirmed the important and long-term volumizing, anti-wrinkle, the hydrating activity of this product after one single injection session. The biological outcomes also support product effectiveness in skin structure restoration.
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http://dx.doi.org/10.2147/CCID.S295618DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8126805PMC
May 2021

Learning adaptive representations for entity recognition in the biomedical domain.

J Biomed Semantics 2021 05 17;12(1):10. Epub 2021 May 17.

Fondazione Bruno Kessler, Via Sommarive 18, Trento, 38123, Italy.

Background: Named Entity Recognition is a common task in Natural Language Processing applications, whose purpose is to recognize named entities in textual documents. Several systems exist to solve this task in the biomedical domain, based on Natural Language Processing techniques and Machine Learning algorithms. A crucial step of these applications is the choice of the representation which describes data. Several representations have been proposed in the literature, some of which are based on a strong knowledge of the domain, and they consist of features manually defined by domain experts. Usually, these representations describe the problem well, but they require a lot of human effort and annotated data. On the other hand, general-purpose representations like word-embeddings do not require human domain knowledge, but they could be too general for a specific task.

Results: This paper investigates methods to learn the best representation from data directly, by combining several knowledge-based representations and word embeddings. Two mechanisms have been considered to perform the combination, which are neural networks and Multiple Kernel Learning. To this end, we use a hybrid architecture for biomedical entity recognition which integrates dictionary look-up (also known as gazetteers) with machine learning techniques. Results on the CRAFT corpus clearly show the benefits of the proposed algorithm in terms of F score.

Conclusions: Our experiments show that the principled combination of general, domain specific, word-, and character-level representations improves the performance of entity recognition. We also discussed the contribution of each representation in the final solution.
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http://dx.doi.org/10.1186/s13326-021-00238-0DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8127187PMC
May 2021

Importance of preserving the resident microflora of the skin to improve immunological response.

J Investig Med 2021 10 10;69(7):1386-1387. Epub 2021 May 10.

Human Microbiome Advanced Project (HMAP), Giuliani, Milan, Italy

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http://dx.doi.org/10.1136/jim-2021-001823DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8485132PMC
October 2021

Contrast-induced encephalopathy after abdominal CT examination.

Acta Neurol Belg 2021 Oct 29;121(5):1325-1326. Epub 2021 Apr 29.

Department of Radiology, CTO Hospital, Azienda Ospedaliera dei Colli, Naples, Italy.

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http://dx.doi.org/10.1007/s13760-021-01690-6DOI Listing
October 2021

Effect of commonly used cosmetic preservatives on skin resident microflora dynamics.

Sci Rep 2021 04 22;11(1):8695. Epub 2021 Apr 22.

Human Advanced Microbiome Project-HMAP, Milan, Italy.

Human skin is populated by various microorganisms, the so-called microbiota, such as bacteria, viruses, yeasts, fungi, and archaea. The skin microbiota is in constant contact with the surrounding environment which can alter its eubiotic state. Recently it has been also observed that the application of cosmetic products can alter the balance of the skin microbiota. This effect may be attributed to many factors including the residual activity of the preservatives on the skin. In the present work, we studied the effect of eleven preservatives commonly found in cosmetic products on Propionibacterium acnes, Staphylococcus epidermidis, and Staphylococcus aureus in vitro using 3D skin models and culture-dependent methods. Also, the effect on Histone deacetylase 3 (HDAC3) has been investigated. Among tested combinations, three resulted as the best suitable for restoring a pre-existing dysbiosis since they act moderately inhibiting C. acnes and strongly S. aureus without simultaneously inhibiting the growth of S. epidermidis. The other four combinations resulted as the best suitable for use in topical products for skin and scalp in which it is necessary to preserve the eubiosis of the microbiota. Some of the tested were also able to increase HDAC3 expression. Taking together these data highlight the role of preservatives of skin resident microflora dynamics and could provide a reference for correctly choice preservatives and dosage in cosmetic formulations to preserve or restore homeostasis of skin microbiota.
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http://dx.doi.org/10.1038/s41598-021-88072-3DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8062602PMC
April 2021

MultiGBS: A multi-layer graph approach to biomedical summarization.

J Biomed Inform 2021 04 18;116:103706. Epub 2021 Feb 18.

Swiss AI Lab IDSIA/Istituto Dalle Molle di Studi sull'Intelligenza Artificiale, CH-6962 Lugano, Switzerland. Electronic address:

Automatic text summarization methods generate a shorter version of the input text to assist the reader in gaining a quick yet informative gist. Existing text summarization methods generally focus on a single aspect of text when selecting sentences, causing the potential loss of essential information. In this study, we propose a domain-specific method that models a document as a multi-layer graph to enable multiple features of the text to be processed at the same time. The features we used in this paper are word similarity, semantic similarity, and co-reference similarity, which are modelled as three different layers. The unsupervised method selects sentences from the multi-layer graph based on the MultiRank algorithm and the number of concepts. The proposed MultiGBS algorithm employs UMLS and extracts the concepts and relationships using different tools such as SemRep, MetaMap, and OGER. Extensive evaluation by ROUGE and BERTScore shows increased F-measure values.
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http://dx.doi.org/10.1016/j.jbi.2021.103706DOI Listing
April 2021

Italian Survey for the Evaluation of the Effects of Coronavirus Disease 2019 (COVID-19) Pandemic on Alopecia Areata Recurrence.

Dermatol Ther (Heidelb) 2021 Apr 12;11(2):339-345. Epub 2021 Feb 12.

International Hair Research Foundation (IHRF), Milan, Italy.

Introduction: The inflammation storm involved in coronavirus disease 2019 (COVID-19) infection and worsening and the psychological stress derived from current quarantine conditions can affect the course of many skin and scalp conditions. This study examined the possible effects of COVID-19 on alopecia areata (AA) relapse in patients suffering from these scalp conditions during the pandemic.

Methods: The study was carried out in the form of an observational cross-sectional type using a questionnaire sent by mail to a cohort of patients affected by AA during the pandemic from March 2020 to October 2020.

Results: During the pandemic, AA relapse was reported in 42.5% of the participants who also declared COVID-19 infection, confirmed by nasopharyngeal swab or hematological analysis. The relapse was reported about 2 months later COVID-19 infection (median of 2.14 months) and 74.0% of these participants continue to experience AA symptoms when the survey was proposed. Only 12.5% of participants reported AA relapse in the absence of COVID-19 infection.

Conclusions: The present study reported a significant relapse in patients suffering from AA and infected by COVID-19. This phenomenon could be attributed to the inflammation storm typical of COVID-19 infection and the psychological stress derived from quarantine conditions.
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http://dx.doi.org/10.1007/s13555-021-00498-9DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7880634PMC
April 2021

Factors associated with cattle necropsy submissions in Switzerland, and their importance for surveillance.

Prev Vet Med 2021 Feb 15;187:105235. Epub 2020 Dec 15.

Institute of Animal Pathology, Department of Infectious Diseases and Pathobiology, Vetsuisse Faculty, University of Bern, Bern, Switzerland.

Pathology data have been reported to be important for surveillance, as they are crucial for correctly recognizing and identifying new or re-emerging diseases in animal populations. However, there are no reports in the literature of necropsy data being compared or complemented with other data. In our study, we compared cattle necropsy reports extracted from 3 laboratories with the Swiss fallen stock data and clinical data collected by the association of Swiss Cattle Breeders. The objective was to assess the completeness, validity and representativeness of the necropsy data, as well as evaluate potential factors for necropsy submission and how they can benefit animal health surveillance. Our results showed that, on average, 1% of Swiss cattle that die are submitted for post-mortem examinations. However, different factors influence cattle necropsy submissions, such as the age of the animal, the geographical location and the number of sick and/or dead animals on the farm. There was a median of five animals reported sick and two animals reported dead within 30 days prior to a necropsy submission, providing quantitative evidence of a correlation between on farm morbidity/mortality and post-mortem examination. Our results also showed that necropsy data can help improve the accuracy and completeness of health data for surveillance systems. In this study, we were able to demonstrate the importance of veterinary pathology data for AHS by providing quantitative evidence that necropsied animals are indicative of farms with important disease problems and are therefore critically important for surveillance. Furthermore, thanks to the amount of information provided by combined data sources, the epidemiology (e.g. season, geographic region, risk factors) of potential diseases can be analysed more precisely and help supporting animal health surveillance systems.
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http://dx.doi.org/10.1016/j.prevetmed.2020.105235DOI Listing
February 2021

Duplication of the posterior cerebral artery: two case reports.

Acta Neurol Belg 2020 Nov 7. Epub 2020 Nov 7.

Neuroradiology Service, Department of Radiology, University of Campania "Luigi Vanvitelli", C/o CTO Viale dei Colli Aminei 21, 80131, Naples, Italy.

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http://dx.doi.org/10.1007/s13760-020-01535-8DOI Listing
November 2020

Vascular Closure Devices Attenuate Femoral Access Complications of Primary Percutaneous Coronary Intervention.

J Invasive Cardiol 2020 Oct;32(10):364-370

Santa Casa de Marília, Avenida Vicente Ferreira, 828, Marília - São Paulo, Brazil.

Objectives: To compare severe complications related to radial access and those related to femoral access using vascular closure devices for patients undergoing primary percutaneous coronary intervention (PCI).

Background: Femoral artery access is still used for acute myocardial infarction management; studies comparing state-of-the-art radial and femoral techniques are required to minimize bias regarding the outcomes associated with operator preferences.

Methods: We performed a randomized study comparing radial access with a compression device and anatomic landmark-guided femoral access with a hemostatic vascular closure device. The severe complication rates related to the access site were assessed until hospital discharge. A meta- analysis including studies with comparable populations reporting severe bleeding and major adverse cardiovascular event rates was performed.

Results: A total of 250 patients were included who underwent PCI between January 2016 and February 2019. Mean age was 61.5 ± 12.2 years, 73.2% were men, and 28.4% had diabetes. There were no differences between groups or in vascular access-related severe complication rates (8.0% for femoral group vs 5.6% for radial group; P=.45). Although radial access was associated with decreased vascular complications related to the access site when compared with the femoral approach (relative risk [RR], 0.64; 95% confidence interval [CI], 0.43-0.95), the meta-analysis did not show an impact on severe bleeding (RR, 0.74; 95% CI, 0.37-1.46) or severe cardiovascular adverse events (RR, 0.69; 95% CI, 0.30-1.58).

Conclusions: Compliance with femoral artery puncture techniques and routine use of a vascular closure device promoted low severe complication rates.
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October 2020

approaches for studying the microbiome in Alopecia areata.

J Investig Med 2020 10 21;68(7):1292-1294. Epub 2020 Sep 21.

Human Microbiome Advanced Project, Milan, Italy.

Nowadays, the involvement of the microbiome in human health and many human diseases, including that strictly related to the scalphas been brought to the light. Indeed, more recently, authors highlighted the presence of a significant microbial shift both in nonscarring (Androgenetic alopecia and Alopecia areata) and scarring Alopecias. The advent of novel technologies together with the effort of many scientists in the microbiome field could provide in the nearest future a clearest framework about the strict relationship between human healthiness and symbiotic microorganism resident on different ecosystem of our body. In this view, the use of Omics approaches has to be considered as no longer negligible when studying the microbiome implication in human health and disease.
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http://dx.doi.org/10.1136/jim-2020-001426DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7525785PMC
October 2020

Bioprocessing of Brewers' Spent Grain Enhances Its Antioxidant Activity: Characterization of Phenolic Compounds and Bioactive Peptides.

Front Microbiol 2020 31;11:1831. Epub 2020 Jul 31.

Department of Soil, Plant and Food Science, University of Bari Aldo Moro, Bari, Italy.

Brewers' spent grain (BSG) is the major by-product of the brewing industry which remain largely unutilized despite its nutritional quality. In this study, the effects of fermentation on BSG antioxidant potential were analyzed. A biotechnological protocol including the use of xylanase followed by fermentation with PU1, PRO17, and H46 was used. Bioprocessed BSG exhibited enhanced antioxidant potential, characterized by high radical scavenging activity, long-term inhibition of linoleic acid oxidation and protective effect toward oxidative stress on human keratinocytes NCTC 2544. Immunolabelling and confocal laser microscopy showed that xylanase caused an extensive cell wall arabinoxylan disruption, contributing to the release of bound phenols molecules, thus available to further conversion through lactic acid bacteria metabolism. To clarify the role of fermentation on the antioxidant BSG potential, phenols were selectively extracted and characterized through HPLC-MS techniques. Novel antioxidant peptides were purified and identified in the most active bioprocessed BSG.
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http://dx.doi.org/10.3389/fmicb.2020.01831DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7411387PMC
July 2020

Cloning of the Rice Resistance Gene and Interaction of the Xo1 Protein with the Defense-Suppressing Effector Tal2h.

Mol Plant Microbe Interact 2020 Oct 2;33(10):1189-1195. Epub 2020 Sep 2.

Plant Pathology and Plant-Microbe Biology Section, School of Integrative Plant Science, Cornell University, Ithaca, NY 14853, U.S.A.

The locus in the heirloom rice variety Carolina Gold Select confers resistance to bacterial leaf streak and bacterial blight, caused by pv. and pv. , respectively. Resistance is triggered by pathogen-delivered transcription activator-like effectors (TALEs) independent of their ability to activate transcription and is suppressed by truncated variants called truncTALEs, common among Asian strains. By transformation of the susceptible variety Nipponbare, we show that one of 14 nucleotide-binding, leucine-rich repeat (NLR) protein genes at the locus, with a zinc finger BED domain, is the gene. Analyses of published transcriptomes revealed that the -mediated response is more similar to those mediated by two other NLR resistance genes than it is to the response associated with TALE-specific transcriptional activation of the executor resistance gene and that a truncTALE dampens or abolishes activation of defense-associated genes by . In leaves, fluorescently tagged Xo1 protein, like TALEs and truncTALEs, localized to the nucleus. And endogenous Xo1 specifically coimmunoprecipitated from rice leaves with a pathogen-delivered, epitope-tagged truncTALE. These observations suggest that suppression of Xo1-function by truncTALEs occurs through direct or indirect physical interaction. They further suggest that effector coimmunoprecipitation may be effective for identifying or characterizing other resistance genes.
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http://dx.doi.org/10.1094/MPMI-05-20-0131-SCDOI Listing
October 2020

Topical odorant application of the specific olfactory receptor OR2AT4 agonist, Sandalore , improves telogen effluvium-associated parameters.

J Cosmet Dermatol 2021 Mar 29;20(3):784-791. Epub 2020 Jul 29.

Monasterium Laboratory, Skin and Hair Research Solutions GmbH, Muenster, Germany.

Background: Human hair follicles (HFs) express the olfactory receptor (OR)2AT4, which is selectively stimulated by the synthetic sandalwood-like odorant, Sandalore . In organ-cultured, human scalp HFs, Sandalore prolongs anagen and suppresses apoptosis by up-regulating intrafollicular IGF-1 mediated signaling.

Aims: The objective of this study is to demonstrate whether effects of Sandalore observed ex vivo translate into a clinically relevant effect in patients with telogen effluvium.

Patients/methods: In a randomized, double-blinded, placebo-controlled, clinical trial, 60 female volunteers (18-65 years) affected by telogen effluvium received over a period of 24 weeks treatment with either 1% Sandalore solution (n = 30) or placebo (identically smelling, but non-OR2AT4 activating sandalwood oil n = 30). The study read-out parameters were the degree of hair shedding, hair volume, terminal/vellus hair ratio, anagen/catagen-telogen ratio, and patient self-assessment.

Results: Sandalore 1% ameliorated clinical signs of telogen effluvium, namely it reduced hair shedding, and increased hair volume and the percentage of anagen HFs, the latter two parameters significantly more than placebo when changes were calculated to baseline. Sandalore also increased the ratio of terminal/vellus hairs at week 8. Most of the anti-hair shedding effects were seen after 8 weeks and maintained at week 24. Patient questionnaire showed that verum group patients were more satisfied than the placebo group in regard to the overall results.

Conclusion: This clinical trial supports previous findings of anagen-prolonging effects of Sandalore ex vivo with similar results now reproduced in clinical practice. It also provides proof-of-principle that a topically applied cosmetic odorant acting through HF olfactory receptors can be a therapeutic alternative to treat hair loss disorders characterized by excessive hair shedding such as telogen effluvium.
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http://dx.doi.org/10.1111/jocd.13608DOI Listing
March 2021

Editor's introduction to the special issue of the 6th Biomedical Linked Annotation Hackathon (BLAH6).

Genomics Inform 2020 Jun 24;18(2):e12. Epub 2020 Jun 24.

Center for Convergence Research of Advanced Technologies, Ewha Womans University, Seoul 03760, Korea.

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http://dx.doi.org/10.5808/GI.2020.18.2.e12DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7362940PMC
June 2020

A TAL effector-like protein of an endofungal bacterium increases the stress tolerance and alters the transcriptome of the host.

Proc Natl Acad Sci U S A 2020 07 6;117(29):17122-17129. Epub 2020 Jul 6.

Section of Plant Pathology and Plant-Microbe Biology, Cornell University, Ithaca, NY 14853;

Symbioses of bacteria with fungi have only recently been described and are poorly understood. In the symbiosis of (formerly ) with the fungus , bacterial type III (T3) secretion is known to be essential. Proteins resembling T3-secreted transcription activator-like (TAL) effectors of plant pathogenic bacteria are encoded in the three sequenced spp. genomes. TAL effectors nuclear-localize in plants, where they bind and activate genes important in disease. The Burkholderia TAL-like (Btl) proteins bind DNA but lack the N- and C-terminal regions, in which TAL effectors harbor their T3 and nuclear localization signals, and activation domain. We characterized a Btl protein, Btl19-13, and found that, despite the structural differences, it can be T3-secreted and can nuclear-localize. A gene knockout did not prevent the bacterium from infecting the fungus, but the fungus became less tolerant to cell membrane stress. Btl19-13 did not alter transcription in a plant-based reporter assay, but 15 genes were differentially expressed in comparisons both of the fungus infected with the wild-type bacterium vs. the mutant and with the mutant vs. a complemented strain. Southern blotting revealed genes in 14 diverse isolates. However, banding patterns and available sequences suggest variation, and the phenotype could not be rescued by a gene from a different strain. Our findings support the conclusion that Btl proteins are effectors that act on host DNA and play important but varied or possibly host genotype-specific roles in the - symbiosis.
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http://dx.doi.org/10.1073/pnas.2003857117DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7382252PMC
July 2020

Predictive Metagenomic Profiling, Urine Metabolomics, and Human Marker Gene Expression as an Integrated Approach to Study Alopecia Areata.

Front Cell Infect Microbiol 2020 29;10:146. Epub 2020 Apr 29.

Human Microbiome Advanced Project-HMPA, Giuliani SpA, Milan, Italy.

Involvement of the microbiome in many different scalp conditions has been investigated over the years. Studies on the role of the scalp microbiome in specific diseases, such as those involving hair growth alterations like non-cicatricial [androgenetic alopecia (AGA), alopecia areata (AA)] and cicatricial alopecia lichen planopilaris, are of major importance. In the present work, we highlighted the differences in microbial populations inhabiting the scalp of AA subjects and a healthy sample cohort by using an integrated approach relying on metagenomic targeted 16S sequencing analysis, urine metabolomics, and human marker gene expression. Significant differences in genera abundances ( < 0.05) were found in the hypodermis and especially the dermis layer. Based on 16S sequencing data, we explored the differences in predicted KEGG pathways and identified some significant differences in predicted pathways related to the AA pathologic condition such as flagellar, assembly, bacterial chemotaxis, mineral absorption, ABC transporters, cellular antigens, glycosaminoglycan degradation, lysosome, sphingolipid metabolism, cell division, protein digestion and absorption, and energy metabolism. All predicted pathways were significantly enhanced in AA samples compared to expression in healthy samples, with the exceptions of mineral absorption, and ABC transporters. We also determined the expression of α, , and genes and explored the relationships between human gene expression levels and microbiome composition by Pearson's correlation analysis; here, significant correlations both positive (SOD vs. ) and negative ( and vs. , and ) were highlighted. Finally, we inspected volatile organic metabolite profiles in urinary samples and detected statistically significant differences (menthol, methanethiol, dihydrodehydro-beta-ionone, 2,5-dimethylfuran, 1,2,3,4, tetrahydro-1,5,7-trimethylnapthalene) when comparing AA and healthy subject groups. This multiple comparison approach highlighted potential traits associated with AA and their relationship with the microbiota inhabiting the scalp, opening up novel therapeutic interventions in such kind of hair growth disorders mainly by means of prebiotics, probiotics, and postbiotics.
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http://dx.doi.org/10.3389/fcimb.2020.00146DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7201066PMC
June 2021

Efficacy of Postbiotics in a PRP-Like Cosmetic Product for the Treatment of Alopecia Area Celsi: A Randomized Double-Blinded Parallel-Group Study.

Dermatol Ther (Heidelb) 2020 Jun 11;10(3):483-493. Epub 2020 Apr 11.

Human Advanced Microbiome Project (HMAP), Giuliani SpA, Milan, Italy.

Introduction: Alopecia areata (AA), also known as 'area Celsi', is the second most common form of hair loss affecting the scalp. Newly proposed treatments for AA include low-level light therapy, biologics such as Janus kinase inhibitors and autologous platelet-rich plasma (PRP), which is a well-known "elixir" for hair growth. Bioactive peptides developed through biotechnological applications have been used to overcome the limitations of PRP. More recently, the involvement of microbiota in hair growth disorders, in AA in particular, has been reported, and the usefulness of microbial metabolites, i.e. postbiotics, has been suggested.

Methods: This study was a randomized double-blinded parallel-group study in which 160 persons of both sexes affected by AA and aged between 18 and 60 years were enrolled. The subjects were randomly assigned to a treatment group (group 1), receiving the TR-PRP plus-Celsi cosmetic product, and a placebo group (group 2). The SALT (Severity of Alopecia Tool) score was determined in both groups at baseline and after 2 and 3 months of treatment, and the results compared between groups.

Results: The subjects in group 1 showed a significant change from baseline in SALT score at 2 months of treatment (61.04% ± 3.45%; p < 0.0001), with a further improvement at the end of treatment (3 months) (69.56% ± 4.32%; p < 0.0001). No significant changes from baseline were reported for the subjects in group 2 (T1: 26.45% ± 3.64%; T3: 27.63% ± 7.61%).

Conclusions: The results of this study provide further proof of the efficacy of bioactive peptides that mimick the growth factors present in PRP in subjects affected by AA. They also add to our knowledge of the link between microbiota and hair growth disorders, emphasizing the importance of studies on the microbial community and microbial metabolites as a novel therapeutic approach.
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http://dx.doi.org/10.1007/s13555-020-00369-9DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7211773PMC
June 2020

Coupled blue and red light-emitting diodes therapy efficacy in patients with rosacea: two case reports.

J Med Case Rep 2020 Jan 28;14(1):22. Epub 2020 Jan 28.

International Hair Research Foundation (IHRF), Milan, Italy.

Background: Rosacea is a common inflammatory skin condition affecting approximately 5% of the world population. Therapeutic approaches to rosacea are focused on symptom suppression by means of anti-inflammatory agents. More recently, photodynamic therapy, especially light-emitting diodes, has been introduced as a valid alternative to conventional therapy.

Case Presentation: In the present work, we reported the efficacy and safety of light-emitting diodes therapy combining blue (480 nm) and red (650 nm) light for the treatment of two patients with papulopustular rosacea: a 22-year-old Caucasian woman and a 68-year-old Caucasian man.

Conclusions: This kind of treatment could represent an effective, safer, and well-tolerated approach for the treatment of such conditions.
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http://dx.doi.org/10.1186/s13256-019-2339-6DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6988247PMC
January 2020

Improving spaCy dependency annotation and PoS tagging web service using independent NER services.

Genomics Inform 2019 Jun 24;17(2):e21. Epub 2019 Jun 24.

Institute of Computational Linguistics, University of Zurich, CH-8050 Zurich, Switzerland.

Dependency parsing is often used as a component in many text analysis pipelines. However, performance, especially in specialized domains, suffers from the presence of complex terminology. Our hypothesis is that including named entity annotations can improve the speed and quality of dependency parses. As part of BLAH5, we built a web service delivering improved dependency parses by taking into account named entity annotations obtained by third party services. Our evaluation shows improved results and better speed.
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http://dx.doi.org/10.5808/GI.2019.17.2.e21DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6808626PMC
June 2019

Introduction to BLAH5 special issue: recent progress on interoperability of biomedical text mining.

Genomics Inform 2019 Jun 27;17(2):e12. Epub 2019 Jun 27.

Institute of Computational Linguistics, University of Zurich, Zurich CH-8050, Switzerland.

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http://dx.doi.org/10.5808/GI.2019.17.2.e12DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6808629PMC
June 2019

Natural Language Processing of Clinical Notes on Chronic Diseases: Systematic Review.

JMIR Med Inform 2019 Apr 27;7(2):e12239. Epub 2019 Apr 27.

eHealth Research Group, Fondazione Bruno Kessler Research Institute, Trento, Italy.

Background: Novel approaches that complement and go beyond evidence-based medicine are required in the domain of chronic diseases, given the growing incidence of such conditions on the worldwide population. A promising avenue is the secondary use of electronic health records (EHRs), where patient data are analyzed to conduct clinical and translational research. Methods based on machine learning to process EHRs are resulting in improved understanding of patient clinical trajectories and chronic disease risk prediction, creating a unique opportunity to derive previously unknown clinical insights. However, a wealth of clinical histories remains locked behind clinical narratives in free-form text. Consequently, unlocking the full potential of EHR data is contingent on the development of natural language processing (NLP) methods to automatically transform clinical text into structured clinical data that can guide clinical decisions and potentially delay or prevent disease onset.

Objective: The goal of the research was to provide a comprehensive overview of the development and uptake of NLP methods applied to free-text clinical notes related to chronic diseases, including the investigation of challenges faced by NLP methodologies in understanding clinical narratives.

Methods: Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines were followed and searches were conducted in 5 databases using "clinical notes," "natural language processing," and "chronic disease" and their variations as keywords to maximize coverage of the articles.

Results: Of the 2652 articles considered, 106 met the inclusion criteria. Review of the included papers resulted in identification of 43 chronic diseases, which were then further classified into 10 disease categories using the International Classification of Diseases, 10th Revision. The majority of studies focused on diseases of the circulatory system (n=38) while endocrine and metabolic diseases were fewest (n=14). This was due to the structure of clinical records related to metabolic diseases, which typically contain much more structured data, compared with medical records for diseases of the circulatory system, which focus more on unstructured data and consequently have seen a stronger focus of NLP. The review has shown that there is a significant increase in the use of machine learning methods compared to rule-based approaches; however, deep learning methods remain emergent (n=3). Consequently, the majority of works focus on classification of disease phenotype with only a handful of papers addressing extraction of comorbidities from the free text or integration of clinical notes with structured data. There is a notable use of relatively simple methods, such as shallow classifiers (or combination with rule-based methods), due to the interpretability of predictions, which still represents a significant issue for more complex methods. Finally, scarcity of publicly available data may also have contributed to insufficient development of more advanced methods, such as extraction of word embeddings from clinical notes.

Conclusions: Efforts are still required to improve (1) progression of clinical NLP methods from extraction toward understanding; (2) recognition of relations among entities rather than entities in isolation; (3) temporal extraction to understand past, current, and future clinical events; (4) exploitation of alternative sources of clinical knowledge; and (5) availability of large-scale, de-identified clinical corpora.
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http://dx.doi.org/10.2196/12239DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6528438PMC
April 2019

Scalp bacterial shift in Alopecia areata.

PLoS One 2019 11;14(4):e0215206. Epub 2019 Apr 11.

Giuliani SpA, Milan, Italy.

The role of microbial dysbiosis in scalp disease has been recently hypothesized. However, little information is available with regards to the association between microbial population on the scalp and hair diseases related to hair growth. Here we investigated bacterial communities in healthy and Alopecia areata (AA) subjects. The analysis of bacterial distribution at the genus level highlighted an increase of Propionibacterium in AA subjects alongside a general decrease of Staphylococcus. Analysis of log Relative abundance of main bacterial species inhabiting the scalp showed a significant increase of Propionibacterium acnes in AA subjects compared to control ones. AA scalp condition is also associated with a significant decrease of Staphylococcus epidermidis relative abundance. No significant changes were found for Staphylococcus aureus. Therefore, data from sequencing profiling of the bacterial population strongly support a different microbial composition of the different area surrounded hair follicle from the epidermis to hypodermis, highlighting differences between normal and AA affected the scalp. Our results highlight, for the first time, the presence of a microbial shift on the scalp of patients suffering from AA and gives the basis for a larger and more complete study of microbial population involvement in hair disorders.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0215206PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6459526PMC
January 2020
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