Miracle-dz/UniFAR-FTUs huggingface dataset:
Challenges and Potential in Increasing Lutein Content in Microalgae

Research on enhancing lutein content in microalgae has made significant progress in recent years. However, strategies are needed to address the possible limitations of microalgae as practical lutein producers. The capacity of lutein sequestration may determine the upper limit of cellular lutein content. The preliminary estimation presented in this work suggests that the lutein sequestration capacity of the light-harvesting complex (LHC) of microalgae is most likely below 2% on the basis of dry cell weight (DCW). Due to its nature as a structural pigment, higher lutein content might interfere with the LHC in fulfilling photosynthetic functions. Storing lutein in a lipophilic environment is a mechanism for achieving high lutein content but several critical barriers must be overcome such as lutein degradation and access to lipid droplet to be stored through esterification. Understanding the mechanisms underlying lipid droplet biogenesis in chloroplasts, as well as carotenoid trafficking through chloroplast membranes and carotenoid esterification, may provide insight for new approaches to achieve high lutein contents in algae. In the meantime, building the machinery for esterification and sequestration of lutein and other hydroxyl-carotenoids in model microorganisms, such as yeast, with synthetic biology technology provides a promising option.
Biotechnological Approaches for Genetic Improvement of Lemon (Citrus limon (L.) Burm. f.) against Mal Secco Disease

Among Citrus species, lemon is one of the most susceptible to mal secco disease, a tracheomycosis caused by the mitosporic fungus Plenodomus tracheiphilus, which induces chlorosis followed by leaf drop and progressive desiccation of twigs and branches. Severe infection can cause the death of the plant. Since no effective control strategies are available to efficiently control the pathogen spread, host tolerance is the most desirable goal in the struggle against mal secco disease. To date, both traditional breeding programs and biotechnological techniques were not efficient in developing novel varieties coupling tolerance to mal secco with optimal fruit quality. Furthermore, the genetic basis of host resistance has not been fully deciphered yet, hampering the set-up of marker-assisted selection (MAS) schemes. This paper provides an overview of the biotechnological approaches adopted so far for the selection of mal secco tolerant lemon varieties and emphasizes the promising contribution of marker-trait association analysis techniques for both unraveling the genetic determinism of the resistance to mal secco and detecting molecular markers that can be readily used for MAS. Such an approach has already proved its efficiency in several crops and could represent a valuable tool to select novel lemon varieties coupling superior fruit quality traits and resistance to mal secco.
Air Pollution Increases the Incidence of Upper Respiratory Tract Symptoms among Polish Children

A substantial proportion of airway disease’s global burden is attributable to exposure to air pollution. This study aimed to investigate the association between air pollution, assessed as concentrations of particulate matter PM2.5 and PM10 on the upper respiratory tract symptoms (URTS) in children. A nation-wide, questionnaire-based study was conducted in Poland in winter 2018/2019 in a population of 1475 children, comparing URTS throughout the study period with publicly available data on airborne particulate matter. A general regression model was used to evaluate the lag effects between daily changes in PM10 and PM2.5 and the number of children reporting URTS and their severity. PM10 and PM2.5 in the single-pollutant models had significant effects on the number of children reporting URTS. The prevalence of URTS: “runny nose”, “sneezing” and “cough” was positively associated with 12-week mean PM2.5 and PM10 concentrations. In the locations with the highest average concentration of PM, the symptoms of runny nose, cough and sneezing were increased by 10%, 9% and 11%, respectively, compared to the cities with the lowest PM concentrations. This study showed that moderate-term exposure (12 week observation period) to air pollution was associated with an increased risk of URTS among children aged 3–12 years in Poland. These findings may influence public debate and future policy at the national and international levels to improve air quality in cities and improve children’s health.
Pre- and Post-Migration Influences on Weight Management Behaviours before and during Pregnancy: Perceptions of African Migrant Women in England

The prevalence of overweight/obesity is high among Black women in England, who also face high risks of pregnancy and childbirth complications. This study explored African migrant women’s perceptions of pre- and post-migration influences on their weight-related behaviours and weight management support during pregnancy. Interviews were conducted with women of child-bearing age from Ghana, Nigeria, and Cameroon (n = 23). Data were analysed using thematic analysis. Four themes were identified: changing dietary behaviours after migration, changing physical activity (PA) behaviours after migration, increased discourse on obesity, and weight management advice and support received. Navigating a new food environment, interactions with other populations in England, and the need to socialise influenced changes in dietary behaviours. Participants considered that living in England ‘makes you lazy’ due to its obesogenic environment, while increased discourses on obesity heightened weight awareness. Women struggled to relate to dietary advice from midwives but found PA advice useful. Relatives provided valuable support but could influence unhealthy weight-related practices. There is a need for interventions addressing gaps in weight management support for these women, especially considering their migrant backgrounds and multicultural identities. Further research is needed to understand their unique challenges, and collaborations with relatives could inform the development of effective weight management interventions.
Bone Marrow Multipotent Mesenchymal Stromal Cells as Autologous Therapy for Osteonecrosis: Effects of Age and Underlying Causes

Bone marrow (BM) is a reliable source of multipotent mesenchymal stromal cells (MSCs), which have been successfully used for treating osteonecrosis. Considering the functional advantages of BM-MSCs as bone and cartilage reparatory cells and supporting angiogenesis, several donor-related factors are also essential to consider when autologous BM-MSCs are used for such regenerative therapies. Aging is one of several factors contributing to the donor-related variability and found to be associated with a reduction of BM-MSC numbers. However, even within the same age group, other factors affecting MSC quantity and function remain incompletely understood. For patients with osteonecrosis, several underlying factors have been linked to the decrease of the proliferation of BM-MSCs as well as the impairment of their differentiation, migration, angiogenesis-support and immunoregulatory functions. This review discusses the quality and quantity of BM-MSCs in relation to the etiological conditions of osteonecrosis such as sickle cell disease, Gaucher disease, alcohol, corticosteroids, Systemic Lupus Erythematosus, diabetes, chronic renal disease and chemotherapy. A clear understanding of the regenerative potential of BM-MSCs is essential to optimize the cellular therapy of osteonecrosis and other bone damage conditions.
Deep Learning for the Classification of Non-Hodgkin Lymphoma on Histopathological Images

Simple Summary Histopathological examination of lymph node (LN) specimens allows the detection of hematological diseases. The identification and the classification of lymphoma, a blood cancer with a manifestation in LNs, are difficult and require many years of training, as well as additional expensive investigations. Today, artificial intelligence (AI) can be used to support the pathologist in identifying abnormalities in LN specimens. In this article, we trained and optimized an AI algorithm to automatically detect two common lymphoma subtypes that require different therapies using normal LN parenchyma as a control. The balanced accuracy in an independent test cohort was above 95%, which means that the vast majority of cases were classified correctly and only a few cases were misclassified. We applied specific methods to explain which parts of the image were important for the AI algorithm and to ensure a reliable result. Our study shows that classifications of lymphoma subtypes is possible with high accuracy. We think that routine histopathological applications for AI should be pursued. Abstract The diagnosis and the subtyping of non-Hodgkin lymphoma (NHL) are challenging and require expert knowledge, great experience, thorough morphological analysis, and often additional expensive immunohistological and molecular methods. As these requirements are not always available, supplemental methods supporting morphological-based decision making and potentially entity subtyping are required. Deep learning methods have been shown to classify histopathological images with high accuracy, but data on NHL subtyping are limited. After annotation of histopathological whole-slide images and image patch extraction, we trained and optimized an EfficientNet convolutional neuronal network algorithm on 84,139 image patches from 629 patients and evaluated its potential to classify tumor-free reference lymph nodes, nodal small lymphocytic lymphoma/chronic lymphocytic leukemia, and nodal diffuse large B-cell lymphoma. The optimized algorithm achieved an accuracy of 95.56% on an independent test set including 16,960 image patches from 125 patients after the application of quality controls. Automatic classification of NHL is possible with high accuracy using deep learning on histopathological images and routine diagnostic applications should be pursued.
Mitophagy and Oxidative Stress: The Role of Aging

Mitochondrial dysfunction is a hallmark of aging. Dysfunctional mitochondria are recognized and degraded by a selective type of macroautophagy, named mitophagy. One of the main factors contributing to aging is oxidative stress, and one of the early responses to excessive reactive oxygen species (ROS) production is the induction of mitophagy to remove damaged mitochondria. However, mitochondrial damage caused at least in part by chronic oxidative stress can accumulate, and autophagic and mitophagic pathways can become overwhelmed. The imbalance of the delicate equilibrium among mitophagy, ROS production and mitochondrial damage can start, drive, or accelerate the aging process, either in physiological aging, or in pathological age-related conditions, such as Alzheimer’s and Parkinson’s diseases. It remains to be determined which is the prime mover of this imbalance, i.e., whether it is the mitochondrial damage caused by ROS that initiates the dysregulation of mitophagy, thus activating a vicious circle that leads to the reduced ability to remove damaged mitochondria, or an alteration in the regulation of mitophagy leading to the excessive production of ROS by damaged mitochondria.
Vitamin D: Not Just Bone Metabolism but a Key Player in Cardiovascular Diseases

Vitamin D is the first item of drug expenditure for the treatment of osteoporosis. Its deficiency is a condition that affects not only older individuals but also young people. Recently, the scientific community has focused its attention on the possible role of vitamin D in the development of several chronic diseases such as cardiovascular and metabolic diseases. This review aims to highlight the possible role of vitamin D in cardiovascular and metabolic diseases. In particular, here we examine (1) the role of vitamin D in diabetes mellitus, metabolic syndrome, and obesity, and its influence on insulin secretion; (2) its role in atherosclerosis, in which chronic vitamin D deficiency, lower than 20 ng/mL (50 nmol/L), has emerged among the new risk factors; (3) the role of vitamin D in essential hypertension, in which low plasma levels of vitamin D have been associated with both an increase in the prevalence of hypertension and diastolic hypertension; (4) the role of vitamin D in peripheral arteriopathies and aneurysmal pathology, reporting that patients with peripheral artery diseases had lower vitamin D values than non-suffering PAD controls; (5) the genetic and epigenetic role of vitamin D, highlighting its transcriptional regulation capacity; and (6) the role of vitamin D in cardiac remodeling and disease. Despite the many observational studies and meta-analyses supporting the critical role of vitamin D in cardiovascular physiopathology, clinical trials designed to evaluate the specific role of vitamin D in cardiovascular disease are scarce. The characterization of the importance of vitamin D as a marker of pathology should represent a future research challenge.
Cathepsin K: A Novel Diagnostic and Predictive Biomarker for Renal Tumors

Simple Summary Our understanding of renal tumors has increased in the last years with the description of several novel entities. The expanding morphological spectrum complicates the pathologist’s diagnosis, often requiring immunohistochemical analysis. The role of cathepsin K immunoexpression is widened as a diagnostic tool in several renal tumors. This review describes the usefulness of cathepsin K in the differential diagnosis of renal neoplasms, highlighting the biological knowledge underpinning its expression. Moreover, cathepsin K seems to be a downstream marker of different genetic alterations, with a possible role as a predictive marker that may prospectively guide the development of therapeutic approaches as a molecular target. Abstract Cathepsin K is a papain-like cysteine protease with high matrix-degrading activity. Among several cathepsins, cathepsin K is the most potent mammalian collagenase, mainly expressed by osteoclasts. This review summarizes most of the recent findings of cathepsin K expression, highlighting its role in renal tumors for diagnostic purposes and as a potential molecular target. Indeed, cathepsin K is a recognized diagnostic tool for the identification of TFE3/TFEB-rearranged renal cell carcinoma, TFEB-amplified renal cell carcinoma, and pure epithelioid PEComa/epithelioid angiomyolipoma. More recently, its expression has been observed in a subgroup of eosinophilic renal neoplasms molecularly characterized by TSC/mTOR gene mutations. Interestingly, both TSC mutations or TFE3 rearrangement have been reported in pure epithelioid PEComa/epithelioid angiomyolipoma. Therefore, cathepsin K seems to be a downstream marker of TFE3/TFEB rearrangement, TFEB amplification, and mTOR pathway activation. Given the established role of mTOR inhibitors as a pharmacological option in renal cancers, cathepsin K could be of use as a predictive marker of therapy response and as a potential target. In the future, uropathologists may implement the use of cathepsin K to establish a diagnosis among renal tumors with clear cells, papillary architecture, and oncocytic features.
The Role of ZEB2 in Human CD8 T Lymphocytes: Clinical and Cellular Immune Profiling in Mowat–Wilson Syndrome

The Zeb2 gene encodes a transcription factor (ZEB2) that acts as an important immune mediator in mice, where it is expressed in early-activated effector CD8 T cells, and limits effector differentiation. Zeb2 homozygous knockout mice have deficits in CD8 T cells and NK cells. Mowat–Wilson syndrome (MWS) is a rare genetic disease resulting from heterozygous mutations in ZEB2 causing disease by haploinsufficiency. Whether ZEB2 exhibits similar expression patterns in human CD8 T cells is unknown, and MWS patients have not been comprehensively studied to identify changes in CD8 lymphocytes and NK cells, or manifestations of immunodeficiency. By using transcriptomic assessment, we demonstrated that ZEB2 is expressed in early-activated effector CD8 T cells of healthy human volunteers following vaccinia inoculation and found evidence of a role for TGFß-1/SMAD signaling in these cells. A broad immunological assessment of six genetically diagnosed MWS patients identified two patients with a history of recurrent sinopulmonary infections, one of whom had recurrent oral candidiasis, one with lymphopenia, two with thrombocytopenia and three with detectable anti-nuclear antibodies. Immunoglobulin levels, including functional antibody responses to protein and polysaccharide vaccination, were normal. The MWS patients had a significantly lower CD8 T cell subset as % of lymphocytes, compared to healthy controls (median 16.4% vs. 25%, p = 0.0048), and resulting increased CD4:CD8 ratio (2.6 vs. 1.8; p = 0.038). CD8 T cells responded normally to mitogen stimulation in vitro and memory CD8 T cells exhibited normal proportions of subsets with important tissue-specific homing markers and cytotoxic effector molecules. There was a trend towards a decrease in the CD8 T effector memory subset (3.3% vs. 5.9%; p = 0.19). NK cell subsets were normal. This is the first evidence that ZEB2 is expressed in early-activated human effector CD8 T cells, and that haploinsufficiency of ZEB2 in MWS patients had a slight effect on immune function, skewing T cells away from CD8 differentiation. To date there is insufficient evidence to support an immunodeficiency occurring in MWS patients.
Prevalence and Risk Factors of Respiratory Syncytial Virus in Children under 5 Years of Age in the WHO European Region: A Systematic Review and Meta-Analysis

A respiratory syncytial virus (RSV) is the major cause of respiratory tract infection in children under 5 years. However, RSV infection in the European Region of the World Health Organization has not been systematically reviewed. The aim was to determine the prevalence and factors associated with RSV in children under 5 years of age in European regions. A systematic review and meta-analysis was performed. CINAHL, Medline, LILACS, ProQuest, SciELO, and Scopus databases were consulted for studies published in the last 5 years, following Preferred Reporting Items for Systematic Reviews and Meta-analysis guidelines. The search equation was “respiratory syncytial virus AND (newborn OR infant OR child) AND (prevalence OR risk factors)”. Studies reporting the prevalence of RSV were eligible for inclusion in the meta-analysis. A total of 20 articles were included. The meta-analytic prevalence estimation of RSV, with a sample of n = 16,115 children, was 46% (95% CI 34–59%). The main risk factors were age, male gender, winter season, and environmental factors such as cold temperatures, higher relative humidity, high concentrations of benzene, exposure to tobacco, and living in urban areas. Robust age-specific estimates of RSV infection in healthy children should be promoted in order to determine the optimal age for immunization. In addition, it is necessary to analyse in greater depth the potentially predictive factors of RSV infection, to be included in prevention strategies.
Machine Learning and Radiomics Applications in Esophageal Cancers Using Non-Invasive Imaging Methods—A Critical Review of Literature

Simple Summary Non-invasive imaging modalities are commonly used in clinical practice. Recently, the application of machine learning (ML) techniques has provided a new scope for more detailed imaging analysis in esophageal cancer (EC) patients. Our review aims to explore the recent advances and future perspective of the ML technique in the disease management of EC patients. ML-based investigations can be used for diagnosis, treatment response evaluation, prognostication, and investigation of biological heterogeneity. The key results from the literature have demonstrated the potential of ML techniques, such as radiomic techniques and deep learning networks, to improve the decision-making process for EC patients in clinical practice. Recommendations have been made to improve study design and future applicability. Abstract Esophageal cancer (EC) is of public health significance as one of the leading causes of cancer death worldwide. Accurate staging, treatment planning and prognostication in EC patients are of vital importance. Recent advances in machine learning (ML) techniques demonstrate their potential to provide novel quantitative imaging markers in medical imaging. Radiomics approaches that could quantify medical images into high-dimensional data have been shown to improve the imaging-based classification system in characterizing the heterogeneity of primary tumors and lymph nodes in EC patients. In this review, we aim to provide a comprehensive summary of the evidence of the most recent developments in ML application in imaging pertinent to EC patient care. According to the published results, ML models evaluating treatment response and lymph node metastasis achieve reliable predictions, ranging from acceptable to outstanding in their validation groups. Patients stratified by ML models in different risk groups have a significant or borderline significant difference in survival outcomes. Prospective large multi-center studies are suggested to improve the generalizability of ML techniques with standardized imaging protocols and harmonization between different centers.
In Vitro and Clinical Safety Assessment of the Multiple W/O/W Emulsion Based on the Active Ingredients from Rosmarinus officinalis L., Avena sativa L. and Linum usitatissimum L.

The multiple W/O/W emulsion supplemented with the extracts of Rosmarinus officinalis L. , Avena sativa L. and Linum usitatissimum L. was prepared in the study, its active compounds were determined by HPLC and its safety was evaluated in vitro by the means of reconstituted human skin model EpiDerm™ for the assessment of its irritation, phototoxicity and early skin inflammation effects and by the 48 h human skin patch test for its skin irritation and allergenic potential. The microbiological challenge test of W/O/W emulsion was performed to ensure its preservation efficiency. The results showed that the W/O/W emulsion loaded with self-preserving plant-based bio-actives had no irritant potential, was not phototoxic and did not provoke skin inflammation or sensitization and thus could be used as a safe base for cosmetic products. Furthermore, our results demonstrate that the safety evaluation of cosmetic ingredients of natural or organic origin could be easily performed using reconstructed human skin model EpiDerm™ similar to the well-defined chemicals used in the cosmetics industry.