Damage function for poly(vinyl chloride) in heritage collections

Yellowing of plastic objects as a consequence of chemical degradation is a common heritage conservation challenge. In the case of poly(vinyl chloride) elimination of hydrogen chloride leads to the formation of polyene sequences that act as chromophores. The objective of this work was to quantitatively evaluate the rate of degradation observed as yellowing, as relevant to room conditions during long-term storage of heritage collections. Degradation was quantified as increase in the b* colour coordinate during accelerated degradation at 50 and 70 °C as a function of temperature, relative humidity, plasticizer content, and polymer molecular weight. The significance of each variable was investigated with multiple linear regression. Lower temperature, lower relative humidity, higher polymer molecular weight and higher plasticizer content were associated with lower degradation rates. The activation energy of 86 kJ/mol was calculated. The concept of ‘1- °C-equivalent’ is introduced to enable variable prioritisation from a heritage management aspect. The resulting model can be used to shape environmental management guidelines and identify the most vulnerable objects in heritage collections

Machine learning-assisted non-destructive plasticizer identification and quantification in historical PVC objects based on IR spectroscopy

Non-destructive spectroscopic analysis combined with machine learning rapidly provides information on the identity and content of plasticizers in PVC objects of heritage value. For the first time, a large and diverse collection of more than 100 PVC objects in different degradation stages and of diverse chemical compositions was analysed by chromatographic and spectroscopic techniques to create a dataset used to construct classification and regression models. Accounting for this variety makes the model more robust and reliable for the analysis of objects in museum collections. Six different machine learning classification algorithms were compared to determine the algorithm with the highest classification accuracy of the most common plasticizers, based solely on the spectroscopic data. A classification model capable of the identification of di(2-ethylhexyl) phthalate, di(2-ethylhexyl) terephthalate, diisononyl phthalate, diisodecyl phthalate, a mixture of diisononyl phthalate and diisodecyl phthalate, and unplasticized PVC was constructed. Additionally, regression models for quantification of di(2-ethylhexyl) phthalate and di(2-ethylhexyl) terephthalate in PVC were built. This study of real-life objects demonstrates that classification and quantification of plasticizers in a general collection of degraded PVC objects is possible, providing valuable data to collection managers

Sustained release of antimicrobials from double-layer nanofiber mats for local treatment of periodontal disease, evaluated using a new micro flow-through apparatus

Periodontal disease is a widespread chronic condition associated with degradation of periodontal tissues that requires more effective approaches for its treatment. Thus, the aim was to develop a nanodelivery system for local application of antimicrobials, with evaluation in vitro using a newly developed micro flow-through apparatus that simulates local in-vivo conditions in the periodontal pocket: small resting volume, and low gingival crevicular fluid flow rate. We successfully developed a double-layer nanofiber mat composed of a chitosan/ poly(ethylene) oxide nanofiber layer with 30% ciprofloxacin, and a poly(ε-caprolactone) nanofiber layer with 5% metronidazole. The precisely designed composition enabled sustained in-vitro release of the antimicrobials according to their specific drug release mechanisms. The rate-limiting step of ciprofloxacin release was its own low solubility at pH 7.4, when there was excess of solid drug present in the delivery system. In contrast, sustained release of metronidazole was due to slow penetration of dissolution medium through the hydrophobic poly(ε-caprolactone) nanofiber layer. The double-layer nanofiber mat developed showed antibacterial activity against Escherichia coli and Aggregatibacter actinomycetemcomitans based on plate antibiogram assays. The antimicrobial concentrations released from the nanofiber mats determined using the developed apparatus were above the minimal inhibitory concentrations against the periodontal pathogens for up to 7 days, which is valuable information for prediction of the efficacy of the nanodelivery system. Although this apparatus was specifically designed for characterization of formulations associated with treatments for periodontal disease, its applicability is much wide, as for development of any delivery system for application at target sites that have similar local conditions

Effect of concomitant medications with immune-modulatory properties on the outcomes of patients with advanced cancer treated with immune checkpoint inhibitors: development and validation of a novel prognostic index

Background: Concomitant medications are known to impact on clinical outcomes of patients treated with immune checkpoint inhibitors (ICIs). We aimed weighing the role of different concomitant baseline medications to create a drug-based prognostic score. Methods: We evaluated concomitant baseline medications at immunotherapy initiation for their impact on objective response rate (ORR), progression-free survival (PFS) and overall survival (OS) in a single-institution cohort of patients with advanced cancer treated with ICIs (training cohort, N = 217), and a drug-based prognostic score with the drugs resulting significantly impacting the OS was computed. Secondly, we externally validated the score in a large multicenter external cohort (n = 1012). Results: In the training cohort (n = 217), the median age was 69 years (range: 32–89), and the primary tumours were non–small-cell lung cancer (70%), melanoma (14.7%), renal cell carcinoma (9.2%) and others (6%). Among baseline medications, corticosteroids (hazard ratio [HR] = 2.3; 95% confidence interval [CI]: 1.60–3.30), systemic antibiotics (HR = 2.07; 95% CI: 1.31–3.25) and proton-pump inhibitors (PPIs) (HR = 1.57; 95% CI: 1.13–2.18) were significantly associated with OS. The prognostic score was calculated using these three drug classes, defining good, intermediate and poor prognosis patients. Within the training cohort, OS (p < 0.0001), PFS (p < 0.0001) and ORR (p = 0.0297) were significantly distinguished by the score stratification. The prognostic value of the score was also demonstrated in terms of OS (p < 0.0001), PFS (p < 0.0001) and ORR (p = 0.0006) within the external cohort. Conclusion: Cumulative exposure to corticosteroids, antibiotics and PPIs (three likely microbiota-modulating drugs) leads to progressively worse outcomes after ICI therapy. We propose a simple score that can help stratifying patients in routine practice and clinical trials of ICIs

Wheat seed embryo excision enables the creation of axenic seedlings and Koch’s postulates testing of putative bacterial endophytes

Early establishment of endophytes can play a role in pathogen suppression and improve seedling development. One route for establishment of endophytes in seedlings is transmission of bacteria from the parent plant to the seedling via the seed. In wheat seeds, it is not clear whether this transmission route exists, and the identities and location of bacteria within wheat seeds are unknown. We identified bacteria in the wheat (Triticum aestivum) cv. Hereward seed environment using embryo excision to determine the location of the bacterial load. Axenic wheat seedlings obtained with this method were subsequently used to screen a putative endophyte bacterial isolate library for endophytic competency. This absence of bacteria recovered from seeds indicated low bacterial abundance and/or the presence of inhibitors. Diversity of readily culturable bacteria in seeds was low with 8 genera identified, dominated by Erwinia and Paenibacillus. We propose that anatomical restrictions in wheat limit embryo associated vertical transmission, and that bacterial load is carried in the seed coat, crease tissue and endosperm. This finding facilitates the creation of axenic wheat plants to test competency of putative endophytes and also provides a platform for endophyte competition, plant growth, and gene expression studies without an indigenous bacterial background

Evaluation of COVID-19 impact on DELAYing diagnostic-therapeutic pathways of lung cancer patients in Italy (COVID-DELAY study): fewer cases and higher stages from a real-world scenario

Introduction: COVID-19 has disrupted the global health care system since March 2020. Lung cancer (LC) patients (pts) represent a vulnerable population highly affected by the pandemic. This multicenter Italian study aimed to evaluate whether the COVID-19 outbreak had an impact on access to cancer diagnosis and treatment of LC pts compared with pre-pandemic time. Methods: Consecutive newly diagnosed LC pts referred to 25 Italian Oncology Departments between March and December 2020 were included. Access rate and temporal intervals between date of symptoms onset and diagnostic and therapeutic services were compared with the same period in 2019. Differences between the 2 years were analyzed using the chi-square test for categorical variables and the Mann\u2013Whitney U test for continuous variables. Results: A slight reduction ( 126.9%) in newly diagnosed LC cases was observed in 2020 compared with 2019 (1523 versus 1637, P = 0.09). Newly diagnosed LC pts in 2020 were more likely to be diagnosed with stage IV disease (P < 0.01) and to be current smokers (someone who has smoked more than 100 cigarettes, including hand-rolled cigarettes, cigars, cigarillos, in their lifetime and has smoked in the last 28 days) (P < 0.01). The drop in terms of new diagnoses was greater in the lockdown period (percentage drop 1212% versus 123.2%) compared with the other months included. More LC pts were referred to a low/medium volume hospital in 2020 compared with 2019 (P = 0.01). No differences emerged in terms of interval between symptoms onset and radiological diagnosis (P = 0.94), symptoms onset and cytohistological diagnosis (P = 0.92), symptoms onset and treatment start (P = 0.40), and treatment start and first radiological revaluation (P = 0.36). Conclusions: Our study pointed out a reduction of new diagnoses with a shift towards higher stage at diagnosis for LC pts in 2020. Despite this, the measures adopted by Italian Oncology Departments ensured the maintenance of the diagnostic-therapeutic pathways of LC pts

Conservation and Diversity of Seed Associated Endophytes in Zea across Boundaries of Evolution, Ethnography and Ecology

Endophytes are non-pathogenic microbes living inside plants. We asked whether endophytic species were conserved in the agriculturally important plant genus Zea as it became domesticated from its wild ancestors (teosinte) to modern maize (corn) and moved from Mexico to Canada. Kernels from populations of four different teosintes and 10 different maize varieties were screened for endophytic bacteria by culturing, cloning and DNA fingerprinting using terminal restriction fragment length polymorphism (TRFLP) of 16S rDNA. Principle component analysis of TRFLP data showed that seed endophyte community composition varied in relation to plant host phylogeny. However, there was a core microbiota of endophytes that was conserved in Zea seeds across boundaries of evolution, ethnography and ecology. The majority of seed endophytes in the wild ancestor persist today in domesticated maize, though ancient selection against the hard fruitcase surrounding seeds may have altered the abundance of endophytes. Four TRFLP signals including two predicted to represent Clostridium and Paenibacillus species were conserved across all Zea genotypes, while culturing showed that Enterobacter, Methylobacteria, Pantoea and Pseudomonas species were widespread, with γ-proteobacteria being the prevalent class. Twenty-six different genera were cultured, and these were evaluated for their ability to stimulate plant growth, grow on nitrogen-free media, solubilize phosphate, sequester iron, secrete RNAse, antagonize pathogens, catabolize the precursor of ethylene, produce auxin and acetoin/butanediol. Of these traits, phosphate solubilization and production of acetoin/butanediol were the most commonly observed. An isolate from the giant Mexican landrace Mixteco, with 100% identity to Burkholderia phytofirmans, significantly promoted shoot potato biomass. GFP tagging and maize stem injection confirmed that several seed endophytes could spread systemically through the plant. One seed isolate, Enterobacter asburiae, was able to exit the root and colonize the rhizosphere. Conservation and diversity in Zea-microbe relationships are discussed in the context of ecology, crop domestication, selection and migration