Search Results (212)

Tuberculosis (TB) is still a significant public health threat, with rising drug resistance and high incidence in multiple areas worldwide. In the search for novel antitubercular agents, this study explores the application of a bioactivity-guided molecular networking approach to identify bioactive compounds from seven plant species (Curatella americana, Davilla nitida, Dipteryx punctata, Indigofera suffruticosa, Quassia amara, Tetradenia riparia, and Zingiber zerumbet) collected in French Guiana. Using ultrasound-assisted extraction followed by liquid–liquid partitioning and UHPLC-HRMS/MS analysis, a library of 72 samples was tested against Mycobacterium tuberculosis. The non-polar fractions from Indigofera suffruticosa, Tetradenia riparia, and Zingiber zerumbet showed the highest activity. The integration of metabolomic and bioassay data on molecular networks allowed the prioritization and annotation of active compounds, revealing flavonoids as contributors to the antitubercular activity of the active samples. In addition, the use of computational tools such as GNPS, SIRIUS, and TIMA-R enabled dereplication and increased the confidence in the structural prediction of active metabolites. This approach demonstrated its potential in accelerating the identification of both known and novel bioactive compounds without requiring exhaustive isolation, offering a robust strategy for natural product-based drug development against TB. Full article

Background: Accurate estimation of mortality is essential for effective public health planning, policymaking, and monitoring of health interventions. In Ghana, multiple data sources are used to estimate mortality, including civil registration systems, household surveys, census data, and health and demographic surveillance systems. This scoping review explores the existing sources of mortality data in Ghana, examining their challenges and opportunities. Methods: Using Arksey and O’Malley’s framework, we identified peer-reviewed and grey literature from Ghana Health Service, Ministry of Health, Ghana Statistical Service, WHO, and the United Nations. We selected studies published between 2000 and 2024 that focused on mortality estimation in Ghana. Data was extracted and synthesized into key themes: data sources, challenges, and opportunities. Results: Six major data sources on mortality were identified: Civil Registration and Vital Statistics (CRVS), census data, Demographic and Health Surveys (DHS), Health and Demographic Surveillance Systems (HDSS), Facility-Based Health Information Systems (HMIS), modeled estimates from the Global Burden of Disease (GBD) and from the United Nations Department of Economic and Social Affairs (UN DESA). Key challenges include under-registration of deaths (CRVS and HMIS), recall bias (DHS, census), limited geographic coverage (HDSS), inconsistencies in cause-of-death classification (HMIS, HDSS), and lack of local geographic coverage (GBD, UN DESA, DHS). Nonetheless, benefits include longitudinal follow-up (HDSS), local coverage and ownership (CRVS, HMIS) and international comparability (GBD, UN DESA, DHS). Conclusions: Mortality estimation in Ghana is supported by diverse but fragmented data sources. Strengthening the CRVS and HMIS systems, integrating multiple data streams, standardizing methodologies, and enhancing institutional partnership are essential steps toward improving data quality and coverage. This review provides recommendations for improvement towards better quality estimations of mortality in Ghana. Full article

Background/Objectives: The burden of chronic obstructive pulmonary disease (COPD) in people who experience frequent moderate/severe exacerbations and frequent productive cough (FPC) while receiving triple inhaled therapy (TT) is poorly described. We aimed to examine clinical characteristics and patient-centric burden of this population. Methods: Data were drawn from the Adelphi COPD Disease-Specific Programme (DSP)™, a multinational cross-sectional survey on COPD (July 2022–January 2023). Patient characteristics and physician perceptions were described for the overall COPD cohort and subsets of those who were current/former Smokers, with ≥2 moderate or ≥1 severe Exacerbation(s) in the prior year while receiving TT and with FPC (SET+FPC) or without FPC (SET w/o FPC). Results: Of the overall cohort (N = 4372), 9.1% (n = 399) patients qualified for inclusion in the SET+FPC cohort; the mean (SD) age was 64.7 (10.9) and 69.1 (9.2) years, respectively. For the overall and SET+FPC cohorts, the mean (SD) number of exacerbations (prior year) was 1.1 (1.4) and 2.5 (1.4), respectively; median post-bronchodilator forced expiratory volume in 1 s (FEV1% predicted) was 68.0% and 49.0%, respectively, and physician-reported dyspnea grade (based on the modified Medical Research Council Dyspnea Scale) was ≥2 in 36.2% and 78.2%, respectively. Physicians were satisfied with COPD control in 76.1% of the overall and 39.6% of the SET+FPC cohorts. Conclusions: People with COPD who experience frequent moderate/severe exacerbations and FPC while receiving TT have substantial clinical and patient-centric burden and extensive unmet medical needs, suggesting inadequate disease control with current standard-of-care therapies. Full article

The distribution of iron oxide (FeO) across the lunar surface is a key parameter for reconstructing the Moon’s geological evolution and evaluating its in situ resource potential for future exploration. This study applies a spectral-based approach to estimate FeO concentrations using remote sensing reflectance data combined with a Random Forest (RF) regression model. The model was trained on a dataset comprising 89 lunar samples from the Reflectance Experiment Laboratory (RELAB) database, supplemented with compositional data from Apollo samples available via the Lunar Sample Compendium and reflectance spectra from the Clementine mission. Spectral data spanning the visible to shortwave infrared range (415–2780 nm) were analysed, with diagnostic absorption features centred around 950 nm, typically associated with Fe²⁺. Model validation was conducted against FeO estimates from independent nearside locations not included in the training set, as reported by an external remote sensing study. The trained model was also applied to produce a new global FeO abundance map, demonstrating strong spatial consistency with recent high-resolution reference datasets. These results confirm the model’s predictive accuracy and support the use of legacy multispectral data for large-scale lunar geochemical mapping. This work highlights the potential of combining machine learning techniques, such as Random Forest, with remote sensing data to enhance lunar surface composition analysis, supporting the planning of future exploration and resource utilisation missions. Full article

Ninety-five-year-old Doris Held, a great niece of Sigmund Freud, has been convening the Shakespeare Reading Group in Northampton, Massachusetts, my hometown, since she moved here in 2016. In the following essay, which is a personal response to my experience of this group of Shakespearean readers, to Doris Held, and to the work of Shakespeare in general, I attempt to chart the full impact of the Bard’s work on my life and on the world around me. I am neither a scholar nor a historian. In a true sense, I am a bystander Shakespearean, who has received deep reward and benefit from the experience, but it is Doris Held and her group who opened my eyes to the precise nature of this unexamined reward. Doris brought the spirit of the group from Cambridge, Massachusetts, where she had been a dues-paying member for decades of something called the Old Cambridge Shakespeare Association, which itself dates to 1880. My wife Debra and I attended the first meeting in Northampton more than a decade ago, and we have been receiving emails from Doris four times a year ever since. While these communications often induce guilt, they invariably lead to pleasures that I would never want to relinquish. That is a complicated dynamic in my routine, and I try to grapple with its ebb and flow in the pages that follow. Each time I get one, I have a version of the same conversation in my head. Is Doris still doing this? Haven’t they done all the plays by now? All things considered, wouldn’t they—and I—rather be home watching a true crime documentary about Gaby Petito on Netflix? What the hell is William Shakespeare to me anyway? At this point, if I’m honest, Shakespeare is Doris. The experience with this group led me in two directions. One took me back to my now long-ago history with Shakespeare’s work as an actor in college. The other took me via historical research into the prehistory of Doris Held’s previous Shakespeare group in Cambridge, Massachusetts. The two paths gave me a deeper grasp of the influence of his work across the world and on my own life. Full article

With the great Clementine Gnomon in St. Maria degli Angeli, a 45 m pinhole meridian line, built in 1700–1702 upon the will of Pope Clemens XI, Francesco Bianchini inaugurated the Roman tradition of solar astrometry. We analyze two thousand dedicated observations at the Clementine Gnomon between 2018 and 2025, with solar altitudes from 20° to 71° and in various meteorological conditions, in order to assess the observational uncertainties on the solar diameter and their causes. We compare the meridian diameters measured by Bianchini near the winter solstices of 1701–1702 with the ones measured by Sigismondi in 2018–2025, reporting the observational errorbars per single measure and the systematic diminutions of the observed diameters with respect to the ephemerides, due to the turbulence and image contrast loss. Simulated datasets based on our measured uncertainties show that pinhole meridian lines cannot resolve solar diameter variations smaller than 1″ over 80 years. These limitations prevent tighter constraints on solar evolution across centuries using such instruments. Full article

This study investigates the impact of rootstock selection on the essential oil (EO) composition of clementine mandarin (Citrus clementina Hort. ex Tan.) var. SRA 63 cultivated in southern Greece. EOs were extracted from the peel and leaves of trees grafted on four commonly used rootstocks: Cleopatra mandarin, sour orange, Troyer citrange, and Swingle citrumelo. The GC-MS analysis revealed significant qualitative and quantitative differences in EO profiles across the different rootstock combinations. In peel EOs, limonene was the dominant compound, particularly in trees grafted onto Cleopatra mandarin and Swingle citrumelo, while Troyer citrange favored a more diverse chemical profile rich in oxygenated monoterpenes, sesquiterpenes, and aldehydes. Leaf EOs were characterized by high levels of sabinene, linalool, and limonene, with Swingle citrumelo promoting sabinene production and Troyer citrange enhancing limonene content and sesquiterpene diversity. Sour orange showed an intermediate effect, increasing both compound diversity and abundance. These results underscore the critical role played by rootstock in modulating the biosynthesis of volatile compounds, likely through physiological and molecular interactions with the scion. These findings offer valuable insights into optimizing EO yield and quality in citriculture and support the broader goal of valorizing Citrus by-products through targeted agricultural practices. This research contributes to the implementation of targeted agricultural practices (rootstock choice) for the development of high-value Citrus-based products with specific quality traits. Full article

This study compares the antioxidant properties and phytochemical profiles of three pairs of widely used medicinal plant species to their counterparts from Provence, France: Arnica montana with Pentanema montanum (formerly known as Inula montana), Helichrysum italicum with Helichrysum stoechas, and Satureja hortensis with Satureja montana. Phytochemical composition has been investigated using UHPLC-HRMS/MS and molecular networking, revealing chemical profiles dominated by phenylpropanoids and flavonoids, with lignans, sesquiterpene lactones, or polyketides aside. Well-plate DPPH/ABTS assays were used to evaluate the antioxidant activity of extracts, and post-column assays were used to identify antioxidant compounds. The three Provence species demonstrated comparable or superior antioxidant activities to their counterparts, primarily attributed to phenolic compounds such as mono- and di-caffeoylquinic acids, quercetagetin-7-O-glucoside, and myricetin acetylhexoside. These findings show the potential of Provence species to be substituted for some overharvested medicinal plants. This research supports biodiversity conservation while promoting the integration of these local species into pharmaceutical, nutraceutical, cosmetic, and food industries. Full article

Introduction: Cognitive impairment (CI) is recognized as a very frequent feature of persons with multiple sclerosis (pwMSs). Multiple studies have demonstrated the effectiveness of cognitive rehabilitation (CR) in improving CI linked to cerebral functional connectivity facilitation and increased strategies to cope with daily living activities. Nevertheless, there is considerable heterogeneity in the methodologies and protocols proposed to pwMSs. Aim: This study aimed to establish a current state of CR for pwMSs, among different types of healthcare providers (HCPs) in France. Methods: A Web-based survey was conducted between March and September 2024 among HCPs involved in the care of pwMSs. Results: One hundred and one HCPs involved in the care of pwMSs participated in this survey. CR was considered efficient by 97% of HCPs, especially when multimodal. Based on the responses, CR is proposed mainly following cognitive complaints, for moderate or severe cognitive disorders, and at the onset of the disease (45%). HCPs mentioned several obstacles to the implementation of CR, notably the cost of remediation (37%), and the lack of availability of both professionals (58%) and patients (51%). Conclusions: This rehabilitation requires specific tools combined with psychoeducative advice provided by multidisciplinary HCPs. Full article

The production of advanced therapy medicinal products (ATMP) is a long and highly technical process, resulting in a high cost per dose, which reduces the number of eligible patients. There is a critical need for a closed and sample-free monitoring system to perform the numerous quality controls required. Current monitoring methods are not optimal, mainly because they require the system to be opened up for sampling and result in material losses. White light spectroscopy has emerged as a technique for sample-free control compatible with closed systems. We have recently proposed its use to monitor cultures of CEM-C1 cell lines. In this paper, we apply this method to T-cells isolated from healthy donor blood samples. The main differences between cell lines and human primary T-cells lie in the slightly different shape of their absorption spectra and in the dynamics of cell expansion. T-cells do not multiply exponentially, resulting in a non-constant generation time. Cell expansion is described by a power-law model, which allows for the definition of instantaneous generation times. A correlation between the linear asymptotic behavior of these generation times and the initial cell concentration leads to the hypothesis that this could be an early predictive marker of the final culture concentration. To the best of our knowledge, this is the first time that such concepts have been proposed. Full article

The valorization of citrus peel byproducts presents a sustainable and innovative approach to reducing food waste while improving the nutritional content of fruit-based products. Citrus peels, a significant byproduct of the fruit juice industry, are abundant in bioactive compounds with recognized health benefits and functional properties, making them particularly suitable for jam production. The global citrus industry generates substantial amounts of waste, with peels accounting for approximately 50% of the total fruit mass. Conventional disposal methods often result in environmental concerns and the underutilization of valuable bioresources. This study aims to investigate the potential of incorporating citrus peel into jam formulations as a means of enhancing their nutritional and functional properties. Jams were prepared using a traditional processing technique (TP) incorporating citrus peel. The experimental jam variants included pomelo peel jam (PPJ), lime peel jam (LiPJ), lemon peel jam (LePJ), clementine peel jam (CPJ), orange peel jam (OPJ), and grapefruit peel jam (GPJ). All jam samples were subjected to comprehensive analyses, including assessments of chemical composition, total soluble solids (TSSs), titrable acidity (g/100 g acid citric), macro- and microelement contents, total phenolic content (TPC), total flavonoid content (TFC), and antioxidant activity using the FRAP assay. The study revealed high levels of biologically active compounds, such aspolyphenols, flavonoids, and vitamin C, in the jams, highlighting their antioxidant properties and potential health benefits. Among the jams, lemon peel jam (LePJ) exhibited the highest antioxidant activity and polyphenol content, making it a superior choice in terms of functional benefits. In terms of sensory analysis, orange peel jam (OPJ) was the most favored by consumers, demonstrating its high acceptability and potential for market success. Full article

Objective: This review provides an overview of the current knowledge regarding the mechanisms of action of AGuIX, a clinical-stage theranostic nano-radiosensitizer composed of gadolinium. It covers the steps following the administration, from the internalization in tumor cells to the interaction with X-rays and the subsequent physical, chemical, biological, and immunological events. Results: After intravenous injection, AGuIX accumulates in tumors through the enhanced permeability and retention (EPR) effect, and its specific retention properties allow its persistence in tumors for several days. At the cellular level, the nanomedicine is internalized by endocytic processes and mainly located in the cytoplasm, especially in lysosomes. AGuIX enhances the effects of radiotherapy (RT) at several levels, starting from radiation–matter interactions to a chemical stage of reactive oxygen species (ROS) production, followed by a cascade of biological events leading to tumor cell death and immune response. Indeed, AGuIX induces a local increase in radiation dose deposition through the emission of Auger electrons, leading to a subsequent increase in ROS generation. AGuIX also impacts RT-induced biological mechanisms, including DNA damage and cell death mechanisms such as apoptosis, autophagic cell death, and ferroptosis. Last, the combination of AGuIX and RT stimulates an antitumor immune response through the induction of immunogenic cell death (ICD), the activation of dendritic and T cells, and the reprogramming of tumor-associated macrophages (TAMs) into a pro-inflammatory phenotype. Conclusions: AGuIX is a clinical-stage nanoparticle (NP) intravenously administered with pan-cancer potential due to its specific biodistribution properties and a strong ability to amplify RT-induced mechanisms. Full article

Chronic intermittent hypoxia (IH) is one of the hallmark features of obstructive sleep apnea (OSA) and adversely affects neurocognitive and behavioral functioning. However, how the duration of IH correlates with its deleterious effects remains unexplored. We aimed to assess the effects of IH over a prolonged period of time mimicking untreated OSA. Male C57Bl/6J mice were exposed to IH for 96 weeks. Sleep activity was acquired using a piezoelectric system. Novel object recognition (NOR) and the elevated plus maze test (EPMT) were conducted as measures of cognitive function and anxiety, respectively. Brain inflammation was evaluated by a panel of inflammation marker assays. All tests were performed after 16 and 96 weeks of IH exposure. After 96 weeks, sleep percentages during the dark phase decreased in both IH and room air (RA) compared to 16-week exposure (RA: p = 0.0214; IH: p = 0.0188). In addition to age-dependent declines in NOR performance, the mice after 96 weeks of IH exposure had lower NOR preference scores than RA controls (p = 0.0070). The time spent in open arms of the EPMT was reduced in mice exposed to IH compared to RA. Inflammatory marker expression increased in IH-exposed mice. Thus, aging and IH induce similar alterations in sleep, cognition, and neuroinflammation. However, the effects of aging are exacerbated by concurrent IH, suggesting that OSA is a disease associated with an acceleration in biological aging. Full article

Pharmaceutical pollution of surface waters has emerged as a significant environmental health concern worldwide. In this study, we investigated the presence and concentration of pharmaceuticals in aquatic environments within Vhembe District Municipality, South Africa. To achieve this, grab samples of water were collected from various locations across the Thulamela Local Municipality encompassing rivers, streams, and dams. A targeted solid-phase extraction method with ultra-high-pressure liquid chromatography coupled with quadrupole time-of-flight mass spectrometry (UHPLC-QTOF-MS/MS) was used to screen, detect, and quantify 98 pharmaceutical compounds and caffeine in the collected water samples. The findings revealed the presence of a range of pharmaceutical compounds, including the antiretrovirals nevirapine and lopinavir, the anticonvulsant/antiepileptic carbamazepine, and the analgesic and antipyretic acetaminophen. The central nervous system stimulant caffeine was also detected in various water bodies across the region. The presence and concentrations of the pharmaceuticals varied across different water bodies, with nevirapine present at nine sites out of twenty-one (up to 166 ng/L), lopinavir at two sites (up to 42 ng/L), carbamazepine at one site (21 ng/L), and acetaminophen at two sites with the highest concentration of 427 ng/L. Caffeine was present at 15 sites (up to 975 ng/L). This study provides valuable insights into pharmaceutical pollution in surface water resources from one of South Africa’s rural areas, Vhembe District Municipality. It contributes to the monitoring data required to find sustainable solutions to the problem of pollutants of emerging concern in aquatic environments worldwide. Full article

In this study, chitosan (CH) was loaded with spearmint (S) essential oil nanoemulsion (EO) to provide antifungal properties during the postharvest storage of soft citrus fruits. (S)-EO (2%) nanoemulsion–CH (0.8%) coatings inhibited 100% of Penicillium italicum and Penicillium digitatum radial mycelial growth and spore germination in vitro. The (S)-EO (2%) nanoemulsion–CH coating (0.8%) enhanced the antifungal activity by achieving 100% inhibition of P. digitatum in soft citrus cultivars ‘Nova’ and ‘Tango’ compared to the control in vivo. However, P. italicum decay was reduced to 33% and 18% in ‘Nova’ and ‘Tango’ soft citrus compared to the control. The (S)-EO (2%)-CH nanoemulsion coating system prepared by high shear homogenization showed a particle size of 252.3 nm and zeta potential of +21.6 mV, indicating changes in molecular interactions and structural reorganization between EO and CH. The polydispersity index values indicated a stable system. pH remained acidic, antifungal activity was favored, and the incorporation of the EO nanoemulsion improved the thermal stability of the CH coating. The optical properties showed less transparency and more opacity. Despite cultivar differences affecting host specificity, the study recommends using a 2% (S)EO nanoemulsion–CH (0.8%) coating instead of synthetic chemicals to extend citrus fruit storage life. Full article