Lung Cancer Surgery in Octogenarians: Implications and Advantages of Artificial Intelligence in the Preoperative Assessment.

The general world population is aging and patients are often diagnosed with early-stage lung cancer at an advanced age. Several studies have shown that age is not itself a contraindication for lung cancer surgery, and therefore, more and more octogenarians with early-stage lung cancer are undergoing surgery with curative intent. However, octogenarians present some peculiarities that make surgical treatment more challenging, so an accurate preoperative selection is mandatory. In recent years, new artificial intelligence techniques have spread worldwide in the diagnosis, treatment, and therapy of lung cancer, with increasing clinical applications. However, there is still no evidence coming out from trials specifically designed to assess the potential of artificial intelligence in the preoperative evaluation of octogenarian patients. The aim of this narrative review is to investigate, through the analysis of the available international literature, the advantages and implications that these tools may have in the preoperative assessment of this particular category of frail patients. In fact, these tools could represent an important support in the decision-making process, especially in octogenarian patients in whom the diagnostic and therapeutic options are often questionable. However, these technologies are still developing, and a strict human-led process is mandatory.

Safety evaluation of the food enzyme preparation D-psicose 3-epimerase from the non-genetically modified Microbacterium foliorum strain SYG27B.

This assessment addresses a food enzyme preparation consisting of the immobilised non-viable cells of the non-genetically modified bacterium identified by the applicant (Samyang Corporation) as Microbacterium foliorum strain SYG27B. This strain produces the enzyme D-psicose 3-epimerase (EC 5.1.3.30). The food enzyme preparation is used for the isomerisation of fructose to produce the speciality carbohydrate D-allulose (synonym D-psicose). Since the hazard identification and characterisation could not be made and the identity of the production organism could not be established, the Panel was unable to complete the assessment of this food enzyme preparation containing D-psicose 3-epimerase.

Anti-interleukin-6 receptor antibody for the treatment of remitting seronegative symmetrical synovitis with pitting oedema: a new outlook?

We present the case of an elderly man with a small-joint polyarthritis, accompanied by pitting oedema, involving hands and feet, raising clinical suspicion of remitting seronegative symmetrical synovitis with pitting oedema (RS3PE). Treatment with corticosteroids was initiated with significant improvement, but unacceptable iatrogeny ensued, and tapering was not possible without disease flare-up. A trial of tocilizumab allowed disease activity control, slow weaning of corticosteroids and, ultimately, its suspension. RS3PE is a rare rheumatological entity, initially thought to be a variant of rheumatoid arthritis (RA), with shared traits with polymyalgia rheumatica (PMR), and other seronegative spondyloarthropathies, thereby implying a shared pathophysiological background. Elevated levels of interleukin 6 (IL-6) are found in patients with RA, have shown to mirror disease activity in PMR and have also been described in the serum and synovial fluid of patients with RS3PE. Tocilizumab, an anti-IL-6 receptor antibody, shows auspicious results in several other rare rheumatic diseases other than RA.

Ceftriaxone-Induced Encephalopathy in a Patient With Chronic Kidney Disease.

Neurotoxicity is an acknowledged side effect of third and fourth-generation cephalosporins, but its occurrence with ceftriaxone is not widely recognized. This article presents a case involving a 56-year-old woman with multiple comorbidities who sought medical attention after experiencing lipothymia. The initial diagnosis suggested a urinary tract infection with acute kidney failure, leading to the initiation of ceftriaxone and hemodialysis. Subsequently, the patient exhibited a progressive deterioration of her neurological state, characterized by agitation and chorea. Metabolic encephalopathy, seizure/nonconvulsive status epilepticus, and acute central nervous system lesions were considered primary differential diagnoses, all of which were subsequently ruled out through thorough investigations. Days later, a remarkable recovery of the patient's neurological state was observed. A retrospective analysis revealed a correlation between the improvement and the fourth day of antimicrobial suspension. Consequently, a presumptive diagnosis of ceftriaxone-induced encephalopathy was made. This unusual case underscores the importance of recognizing the potential for pharmacological encephalopathy, particularly with ceftriaxone, and emphasizes its reversibility upon discontinuation of the implicated drug. Clinicians should remain vigilant to this uncommon adverse effect, promoting timely intervention and improved patient outcomes.

Metabolic and molecular imaging in inflammatory arthritis.

It is known that metabolic shifts and tissue remodelling precede the development of visible inflammation and structural organ damage in inflammatory rheumatic diseases such as the inflammatory arthritides. As such, visualising and measuring metabolic tissue activity could be useful to identify biomarkers of disease activity already in a very early phase. Recent advances in imaging have led to the development of so-called 'metabolic imaging' tools that can detect these changes in metabolism in an increasingly accurate manner and non-invasively.Nuclear imaging techniques such as 18F-D-glucose and fibroblast activation protein inhibitor-labelled positron emission tomography are increasingly used and have yielded impressing results in the visualisation (including whole-body staging) of inflammatory changes in both early and established arthritis. Furthermore, optical imaging-based bedside techniques such as multispectral optoacoustic tomography and fluorescence optical imaging are advancing our understanding of arthritis by identifying intra-articular metabolic changes that correlate with the onset of inflammation with high precision and without the need of ionising radiation.Metabolic imaging holds great potential for improving the management of patients with inflammatory arthritis by contributing to early disease interception and improving diagnostic accuracy, thereby paving the way for a more personalised approach to therapy strategies including preventive strategies. In this narrative review, we discuss state-of-the-art metabolic imaging methods used in the assessment of arthritis and inflammation, and we advocate for more extensive research endeavours to elucidate their full field of application in rheumatology.

Explaining protein-protein interactions with knowledge graph-based semantic similarity.

The application of artificial intelligence and machine learning methods for several biomedical applications, such as protein-protein interaction prediction, has gained significant traction in recent decades. However, explainability is a key aspect of using machine learning as a tool for scientific discovery. Explainable artificial intelligence approaches help clarify algorithmic mechanisms and identify potential bias in the data. Given the complexity of the biomedical domain, explanations should be grounded in domain knowledge which can be achieved by using ontologies and knowledge graphs. These knowledge graphs express knowledge about a domain by capturing different perspectives of the representation of real-world entities. However, the most popular way to explore knowledge graphs with machine learning is through using embeddings, which are not explainable. As an alternative, knowledge graph-based semantic similarity offers the advantage of being explainable. Additionally, similarity can be computed to capture different semantic aspects within the knowledge graph and increasing the explainability of predictive approaches. We propose a novel method to generate explainable vector representations, KGsim2vec, that uses aspect-oriented semantic similarity features to represent pairs of entities in a knowledge graph. Our approach employs a set of machine learning models, including decision trees, genetic programming, random forest and eXtreme gradient boosting, to predict relations between entities. The experiments reveal that considering multiple semantic aspects when representing the similarity between two entities improves explainability and predictive performance. KGsim2vec performs better than black-box methods based on knowledge graph embeddings or graph neural networks. Moreover, KGsim2vec produces global models that can capture biological phenomena and elucidate data biases.

Hyaluronic acid-functionalized graphene-based nanohybrids for targeted breast cancer chemo-photothermal therapy.

Nanomaterials' application in cancer therapy has been driven by their ability to encapsulate chemotherapeutic drugs as well as to reach the tumor site. Nevertheless, nanomedicines' translation has been limited due to their lack of specificity towards cancer cells. Although the nanomaterials' surface can be coated with targeting ligands, such has been mostly achieved through non-covalent functionalization strategies that are prone to premature detachment. Notwithstanding, cancer cells often establish resistance mechanisms that impair the effect of the loaded drugs. This bottleneck may be addressed by using near-infrared (NIR)-light responsive nanomaterials. The NIR-light triggered hyperthermic effect generated by these nanomaterials can cause irreversible damage to cancer cells or sensitize them to chemotherapeutics' action. Herein, a novel covalently functionalized targeted NIR-absorbing nanomaterial for cancer chemo-photothermal therapy was developed. For such, dopamine-reduced graphene oxide nanomaterials were covalently bonded with hyaluronic acid, and then loaded with doxorubicin (DOX/HA-DOPA-rGO). The produced nanomaterials showed suitable physicochemical properties, high encapsulation efficiency, and photothermal capacity. The in vitro studies revealed that the nanomaterials are cytocompatible and that display an improved uptake by the CD44-overexpressing breast cancer cells. Importantly, the combination of DOX/HA-DOPA-rGO with NIR light reduced breast cancer cells' viability to just 23 %, showcasing their potential chemo-photothermal therapy.

Harmonising dietary datasets for global surveillance: methods and findings from the Global Dietary Database.

OBJECTIVE: The Global Dietary Database (GDD) expanded its previous methods to harmonise and publicly disseminate individual-level dietary data from nutrition surveys worldwide. DESIGN: Analysis of cross-sectional data. SETTING: Global. PARTICIPANTS: General population. METHODS: Comprehensive methods to streamline the harmonisation of primary, individual-level 24-h recall and food record data worldwide were developed. To standardise the varying food descriptions, FoodEx2 was used, a highly detailed food classification and description system developed and adapted for international use by European Food Safety Authority (EFSA). Standardised processes were developed to: identify eligible surveys; contact data owners; screen surveys for inclusion; harmonise data structure, variable definition and unit and food characterisation; perform data checks and publicly disseminate the harmonised datasets. The GDD joined forces with FAO and EFSA, given the shared goal of harmonising individual-level dietary data worldwide. RESULTS: Of 1500 dietary surveys identified, 600 met the eligibility criteria, and 156 were prioritised and contacted; fifty-five surveys were included for harmonisation and, ultimately, fifty two were harmonised. The included surveys were primarily nationally representative (59 %); included high- (39 %), upper-middle (21 %), lower-middle (27 %) and low- (13 %) income countries; usually collected multiple recalls/ records (64 %) and largely captured both sexes, all ages and both rural and urban areas. Surveys from low- and lower-middle v. high- and upper-middle income countries reported fewer nutrients (median 17 v. 30) and rarely included nutrients relevant to diet-related chronic diseases, such as n-3 fatty acids and Na. CONCLUSIONS: Diverse 24-h recalls/records can be harmonised to provide highly granular, standardised data, supporting nutrition programming, research and capacity development worldwide.

Intratendinous Ganglion Cyst of the Extensor Indicis: A Case Report.

An intratendinous ganglion cyst is a very rare benign lesion with an unknown etiology. The clinical diagnosis can be difficult as patients may have mild symptoms or impaired hand functionality. Ultrasound and magnetic resonance imaging can differentiate a ganglion cyst from other soft-tissue tumors and tumor-like lesions and provide excellent information on the location of an intratendinous lesion to schedule surgical treatment. We present a case report of a 50-year-old female diagnosed with an intratendinous ganglion cyst of the extensor indicis. She complained of right-hand swelling for three months, which was associated with pain. The US revealed an oval hypoechoic mass with cystic formation at the extensor indicis, measuring 9 x 4 mm, compatible with an intratendinous ganglion cyst. The cyst was excised by enucleation. After surgery, the patient was referred to the Department of Physical and Rehabilitation Medicine for evaluation. She started a rehabilitation programme. The patient presented a favourable clinical evolution with a return to her previous professional activity. However, six months after surgery, the cyst recurred, but with a smaller size and no associated pain.

Safety evaluation of the food enzyme phospholipase A2 from the genetically modified Aspergillus niger strain PLA.

The food enzyme phospholipase A2 (phosphatidylcholine 2-acylhydrolase, EC 3.1.1.4) is produced with the genetically modified Aspergillus niger strain PLA by DSM Food Specialties B.V. The genetic modifications do not give rise to safety concerns. The food enzyme is free from viable cells of the production organism and its DNA. It is intended to be used in the processing of egg and egg products, in the processing of fats and oils by degumming and for the production of modified lecithins (lysolecithin). As residual total organic solids (TOS) are removed in the refined fats and oils during degumming, dietary exposure was calculated only for the remaining two food manufacturing processes. For egg processing, the dietary exposure was estimated to be up to 1.712 mg TOS/kg body weight (bw) per day in European populations. Wet gum can be used to produce lysolecithin with the highest dietary exposure of 1.61 mg TOS/kg bw per day in children at the 95th percentile when used as a food additive. Genotoxicity tests did not raise a safety concern. The systemic toxicity was assessed by a repeated dose 90-day oral toxicity study in rats. The Panel identified a no observed adverse effect level of 1350 mg TOS/kg bw per day, the highest dose tested, which, when compared with the estimated overall dietary exposure, resulted in a margin of exposure of at least 851. A search for the similarity of the amino acid sequence of the food enzyme to those of known allergens was made and no match was found. The Panel considered that the risk of allergic reactions by dietary exposure cannot be excluded, but the likelihood is low. Based on the data provided, the Panel concluded that this food enzyme does not give rise to safety concerns under the intended conditions of use.

A hitchhikers' guide to the terminology of accreditation processes for health professionals and institutions.

Accreditation processes for health care professions are designed to ensure that individuals and programs in these fields meet established standards of quality and effectiveness. The accelerating pace of globalization in the health care professions has increased the need for a shared understanding of the vocabulary of evaluation, assessment, and accreditation. The psychometric principles of valid and reliable assessment are commonly accepted, but the terminology is confusing. We believe that all stakeholders - evaluators, faculty, students but also the community - will benefit from a shared language and common set of definitions. We recognize that not all readers will agree with the definitions we propose, but we hope that this guide will help to ensure clarity, consistency, transparency, and fairness, and that it will promote through the stimulation of a debate greater collaboration across national and international boundaries.

Prevention, protocols, and lab capacity: lessons from a norovirus outbreak in the Algarve.

This brief report presents the findings of an epidemiological investigation into a large-scale outbreak of norovirus gastroenteritis that occurred in a hotel in Algarve, Portugal, in August 2022. A total of 244 cases were reported, primarily affecting Portuguese families, with the parents aged 40-50 years and the children aged 0-19 years. Reported symptoms included vomiting, nausea, abdominal pain, and diarrhoea. Norovirus genotype GI.3 [P3] was detected in stool samples from eight probable cases, while food samples tested negative for norovirus and common pathogenic bacteria. The investigation data collected suggest that the source of the outbreak was likely in the hotel's common areas, with subsequent person-to-person transmission in other areas. The final report emphasizes the importance of improving outbreak prevention and control measures, including the development of a foodborne outbreak investigation protocol, the establishment of an outbreak response team, and the enhancement of regional laboratory capacity.

A Rare First Presentation of Hodgkin's Lymphoma: Symptomatic Pericardial Effusion.

Symptomatic pericardial effusion occurring as the initial manifestation of Hodgkin's lymphoma is exceedingly uncommon, and there are limited documented instances in the available literature. Pericardial effusion can present various differential diagnoses, and among these, malignancy is an important yet less frequently encountered cause. A heightened level of suspicion is crucial for establishing an accurate diagnosis, particularly when the patient's clinical course deviates from the anticipated trajectory. Through this case, we aim to emphasize the significance of considering lymphoproliferative diseases as a pertinent possibility in the differential diagnosis of pericardial effusion. Additionally, we underscore the importance of promptly reaching a diagnosis, as it can help prevent severe complications and enhance the patient's prognosis.

Sulfobetaine methacrylate-coated reduced graphene oxide-IR780 hybrid nanosystems for effective cancer photothermal-photodynamic therapy.

Nanomaterials with near infrared light absorption can mediate an antitumoral photothermal-photodynamic response that is weakly affected by cancer cells' resistance mechanisms. Such nanosystems are commonly prepared by loading photosensitizers into nanomaterials displaying photothermal capacity, followed by functionalization to achieve biological compatibility. However, the translation of these multifunctional nanomaterials has been limited by the fact that many of the photosensitizers are not responsive to near infrared light. Furthermore, the reliance on poly(ethylene glycol) for functionalizing the nanomaterials is also not ideal due to some immunogenicity reports. Herein, a novel photoeffective near infrared light-responsive nanosystem for cancer photothermal-photodynamic therapy was assembled. For such, dopamine-reduced graphene oxide was, for the first time, functionalized with sulfobetaine methacrylate-brushes, and then loaded with IR780 (IR780/SB/DOPA-rGO). This hybrid system revealed a nanometric size distribution, optimal surface charge and colloidal stability. The interaction of IR780/SB/DOPA-rGO with near infrared light prompted a temperature increase (photothermal effect) and production of singlet oxygen (photodynamic effect). In in vitro studies, the IR780/SB/DOPA-rGO per se did not elicit cytotoxicity (viability > 78 %). In contrast, the combination of IR780/SB/DOPA-rGO with near infrared light decreased breast cancer cells' viability to just 21 %, at a very low nanomaterial dose, highlighting its potential for cancer photothermal-photodynamic therapy.

Transmission dynamics of SARS-CoV-2 variants in the Brazilian state of Pará.

Introduction: After three years since the beginning of the pandemic, the new coronavirus continues to raise several questions regarding its infectious process and host response. Several mutations occurred in different regions of the SARS-CoV-2 genome, such as in the spike gene, causing the emergence of variants of concern and interest (VOCs and VOIs), of which some present higher transmissibility and virulence, especially among patients with previous comorbidities. It is essential to understand its spread dynamics to prevent and control new biological threats that may occur in the future. In this population_based retrospective observational study, we generated data and used public databases to understand SARS-CoV-2 dynamics. Methods: We sequenced 1,003 SARS-CoV-2 genomes from naso-oropharyngeal swabs and saliva samples from Pará from May 2020 to October 2022. To gather epidemiological data from Brazil and the world, we used FIOCRUZ and GISAID databases. Results: Regarding our samples, 496 (49.45%) were derived from female participants and 507 (50.55%) from male participants, and the average age was 43 years old. The Gamma variant presented the highest number of cases, with 290 (28.91%) cases, followed by delta with 53 (5.28%). Moreover, we found seven (0.69%) Omicron cases and 651 (64.9%) non-VOC cases. A significant association was observed between sex and the clinical condition (female, p = 8.65e-08; male, p = 0.008961) and age (p = 3.6e-10). Discussion: Although gamma had been officially identified only in December 2020/January 2021, we identified a gamma case from Belém (capital of Pará State) dated May 2020 and three other cases in October 2020. This indicates that this variant was circulating in the North region of Brazil several months before its formal identification and that Gamma demonstrated its actual transmission capacity only at the end of 2020. Furthermore, the public data analysis showed that SARS-CoV-2 dispersion dynamics differed in Brazil as Gamma played an important role here, while most other countries reported a new infection caused by the Delta variant. The genetic and epidemiological information of this study reinforces the relevance of having a robust genomic surveillance service that allows better management of the pandemic and that provides efficient solutions to possible new disease-causing agents.

Safety evaluation of the food enzyme asparaginase from the genetically modified Aspergillus oryzae strain NZYM-SP.

The food enzyme asparaginase (l-asparagine amidohydrolase, EC 3.5.1.1) is produced with the genetically modified Aspergillus oryzae strain NZYM-SP by Novozymes A/S. The genetic modifications do not give rise to safety concerns. The food enzyme is considered free from viable cells of the production organism and its DNA. It is intended to be used to prevent acrylamide formation in food processing. Dietary exposure to the food enzyme-total organic solids (TOS) was estimated to be up to 0.101 mg TOS/kg body weight (bw) per day in European populations. Genotoxicity tests did not indicate a safety concern. The systemic toxicity was assessed by means of a repeated dose 90-day oral toxicity study in rats. The Panel identified a no observed adverse effect level of 880 mg TOS/kg bw per day, the highest dose tested, which, when compared with the estimated dietary exposure, resulted in a margin of exposure of at least 8,713. A search for the similarity of the amino acid sequence of the food enzyme to known allergens was made and no match was found. The Panel considered that a risk of allergic reactions by dietary exposure cannot be excluded, but the likelihood is low. Based on the data provided, the Panel concluded that this food enzyme does not give rise to safety concerns under the intended conditions of use.

Task Force for a rapid response to an outbreak of severe acute hepatitis of unknown aetiology in children in Portugal in 2022.

On 5 April 2022, the United Kingdom reported an increase of cases of severe acute hepatitis of unknown aetiology in children, several needing hospitalisation and some required liver transplant or died. Thereafter, 35 countries reported probable cases, almost half of them in Europe. Facing the alert, on 28 April, Portugal created a multidisciplinary Task Force (TF) for rapid detection of probable cases and response. The experts of the TF came from various disciplines: clinicians, laboratory experts, epidemiologists, public health experts and national and international communication. Moreover, Portugal adopted the European Centre for Disease Prevention and Control (ECDC) and the World Health Organization (WHO) case definition and recommendations. By 31 December 2022, 28 probable cases of severe acute hepatitis of unknown aetiology were reported: 16 male and 17 aged under 2 years. Of these cases, 23 were hospitalised but none required liver transplant or died. Adenovirus was detected from nine of 26 tested cases. No association was observed between adenovirus infection and hospital admission after adjusting for age, sex and region in a binomial regression model. The TF in Portugal may have contributed to increase awareness among clinicians, enabling early detection and prompt management of the outbreak.

T helper type 9 cell response and its role in the neurological clinic of patients with Human T-lymphotropic virus 1.

Human T-lymphotropic virus 1 (HTLV-1) affects 5-10 million individuals worldwide. Most of those infected with this virus remain asymptomatic; however, 0.25%-4% of individuals develop HTLV-1-associated myelopathy/tropical spastic paraparesis (HAM/TSP), while 2%-4% develop adult T-cell leukemia/lymphoma (ATLL). Understanding the immune response inherent in this infection is extremely important. The role of T helper type 1 (Th1) and Th2 cells in HTLV-1 infection is well known; however, exploring the different subtypes of immune responses is also necessary. The role of Th9 cells in HTLV-1 infection and the mechanisms involved in their interference in the pathophysiological process of HAM/TSP is poorly understood. This study aimed to evaluate the expression profiles of PU.1, interferon regulatory factor 4 (IRF-4), and cytokine interleukin-9 (IL-9) during the induction of peripheral immune response and their role in the HTLV-1-infected patients' neurological symptoms. This analytical cross-sectional study was carried out at the Laboratory of Clinical and Epidemiology of Endemic Diseases and the Laboratory of Immunopathology, both from the Tropical Medicine Center at the Federal University of Pará. Assessment of neurological parameters was performed (gait, Expanded Kurtzke Disability State Scale (EDSS) score, upper and lower limb reflexes, Hoffman's sign, Babinski reflex, and clonus reflex). For Th9 cell analysis, peripheral blood samples were collected from HTLV-1-infected patients; then, the lymphomononuclear cells were separated followed by the isolation of messenger ribonucleic acid (mRNA). Complementary deoxyribonucleic acid (cDNA) synthesis each sample was carried out. The gene expression levels of PU.1, IRF-4, and IL-9 as well as those of constitutive genes (glyceraldehyde 3-phosphate dehydrogenase (GAPDH) and ß-actin) were quantified by real-time polymerase chain reaction (qPCR). This study included 81 HTLV-1-infected patients, of whom 47 were asymptomatic, 13 were mono/oligosymptomatic (MOS), and 21 developed HAM/TSP. IL-9 was the least expressed gene among the three studied groups. The MOS group showed the lowest expression levels of PU.1, IRF-4, and IL-9. HAM/TSP patients showed lower IL-9 protein quantification. Negative correlations were found between IL and 9 and EDSS in MOS patients and between PU.1, EDSS, IRF-4, and EDSS in the HAM/TSP group. An association was found between IL and 9 and Babinski reflex in the HAM/TSP group, suggesting that this gene was more highly expressed in patients who did not have this pathological sign. Th9 cells may interfere with the neurological progression of HAM/TSP and act as a protective factor.