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Language proficiency is an important aspect of the social inclusion of young people from a migrant background. However, some researchers noted similarities in the level of inclusion between first‑ and second‑generation children, despite the different linguistic profile. This study attempts to deepen the analysis of this relationship through the answers to a tailor‑made questionnaire given by 135 adolescents attending multi‑cultural schools in Venice. Italian L2 is confirmed as an essential factor for inclusion, but its effect comes more from its role in the construction of cultural identity than from the opportunity to communicate.

Maria Devita,1,2 Rossella De Salvo,1 Adele Ravelli,2 Marina De Rui,2 Alessandra Coin,2 Giuseppe Sergi,2 Daniela Mapelli1 1Department of General Psychology (DPG), University of Padua, Padua, Italy; 2Geriatrics Division, Department of Medicine (DIMED), University of Padua, Padua, ItalyCorrespondence: Maria Devita, Department of General Psychology, Via Venezia 8, Padua, 35128, Italy, Tel +390498218949, Email maria.devita@unipd.itAbstract: Depression is one of the most common mood disorders in the late-life population and is associated with poor quality of life and increased morbidity, disability and mortality. Nevertheless, in older adults, it often remains undetected and untreated. This narrative review aims at giving an overview on the main definitions, clinical manifestations, risk and protective factors for depression in the elderly, and at discussing the main reasons for its under/misdiagnosis, such as cognitive decline and their overlapping symptomatology. A practical approach for the global and multidisciplinary care of the older adult with depression, derived from cross-checking evidence emerging from the literature with everyday clinical experience, is thus provided, as a short and flexible “pocket” guide to orient clinicians in recognizing, diagnosing and treating depression in the elderly.Keywords: late-life depression, older adults, mood disorders, geriatric depression

ED Toffanello,1 EM Inelmen,1 A Imoscopi,1 E Perissinotto,2 A Coin,1 F Miotto,1 LM Donini,3 D Cucinotta,4 M Barbagallo,5 E Manzato,1 G Sergi11Department of Medical and Surgical Sciences, Geriatrics Division and University of Padova, Padova, 2Department of Environmental Medicine and Public Health, University of Padua, Padua, Italy; 3Department of Medical Physiopathology (Food Science Section), University of Roma, La Sapienza, Roma, 4S Orsola Malpighi Hospital, Bologna, 5Geriatric Unit, Department of Internal Medicine and Emerging Diseases, University of Palermo, Palermo, ItalyBackground: Loss of the sense of taste is common among older people. Morbidities and polypharmacy may contribute to the age-related decline in gustatory function. The aims of the present study were to investigate taste perception in elderly hospitalized patients by comparing their taste recognition thresholds with those of healthy, free-living elderly individuals and to identify potential determinants of taste loss.Methods: The participants in this observational study were 55 elderly patients hospitalized in the acute geriatric section of the Department of Medical and Surgical Sciences at Padova University and 41 free-living individuals aged older than 65 years, randomly recruited from elderly people attending mild fitness programs at public gymnasiums in Padova. Data were collected on nutrition, health, cognitive, and functional status for all participants. Gustatory capabilities were assessed using aqueous solutions of sucrose, sodium chloride, citric acid, and quinine hydrochloride (representing sweet, salty, sour, and bitter stimuli, respectively), and taste recognition thresholds were measured in both groups.Results: In comparison with the free-living elderly subjects, those in hospital were significantly less able to recognize the taste of citric acid (P < 0.05). Low citric acid sensitivity was independently associated with advanced age (≥75 years; odds ratio [OR] 3.01, 95% confidence interval [CI] 1.01–9.82), polypharmacy (number of prescribed drugs ≥ 4; OR 2.74, 95% CI 1.01–7.72), and poor nutritional status (as assessed by Mini Nutritional Assessment score < 23.5; OR 5.08, 95% CI 1.76–14.6).Conclusion: Because gustatory impairment may reduce a person's appetite and lead to inadequate dietary intake, compensatory nutritional measures, such as the use of flavor-enhanced foods, should be strongly encouraged, particularly in the hospital setting.Keywords: taste thresholds, taste loss, hospitalized elderly, sour stimuli, polypharmacy, malnutrition

With the increasing use of anti-TNF therapy in inflammatory bowel disease (IBD), a shift of costs has been observed with medication costs replacing hospitalization and surgery as major cost driver. We aimed to explore the evolution of IBD-related costs over two years of follow-up.In total 1,307 Crohn's disease (CD) patients and 915 ulcerative colitis (UC) patients were prospectively followed for two years by three-monthly web-based questionnaires. Changes of healthcare costs, productivity costs and out-of-pocket costs over time were assessed using mixed model analysis. Multivariable logistic regression analysis was used to identify costs drivers. In total 737 CD patients and 566 UC were included. Total costs were stable over two years of follow-up, with annual total costs of €7,835 in CD and €3,600 in UC. However, within healthcare costs, the proportion of anti-TNF therapy-related costs increased from 64% to 72% in CD (p

Elisabetta Marini,1 Roberto Buffa,1 Bruno Saragat,1 Alessandra Coin,2 Elena Debora Toffanello,2 Linda Berton,2 Enzo Manzato,2 Giuseppe Sergi21Department of Environmental and Life Sciences, University of Cagliari, Italy; 2Department of Medicine-DIMED, Geriatrics Section, University of Padua, ItalyPurpose: The aim of this paper is to investigate whether bioelectrical impedance vector analysis (BIVA) can be a suitable technique for the assessment of sarcopenia. We also investigate the potential use of specific BIVA as an indicator of sarcopenic obesity.Subjects and methods: The sample comprised 207 free-living elderly individuals of both sexes, aged 65 to 93 years. Anthropometric and bioelectrical measurements were taken according to standard criteria. The “classic” and “specific” BIVA procedures, which respectively correct bioelectrical values for body height and body geometry, were used. Dual energy X-ray absorptiometry (DXA) was used as the reference method for identifying sarcopenic and obese sarcopenic individuals. Bioelectrical and DXA values were compared using Student’s t-test and Hotelling’s T2 test, as well as Pearson’s correlation coefficient.Results: According to classic BIVA, sarcopenic individuals of both sexes showed higher values of resistance/height (R/H; p < 0.01) and impedance/height (Z/H; p < 0.01), and a lower phase angle (p < 0.01). Similarly, specific BIVA showed significant differences between sarcopenic and nonsarcopenic individuals (men: T2 = 15.7, p < 0.01; women: T2 = 10.7, p < 0.01), with the sarcopenic groups showing a lower specific reactance and phase angle. Phase angle was positively correlated with the skeletal muscle mass index (men: r = 0.52, p < 0.01; women: r = 0.31, p < 0.01). Specific BIVA also recognized bioelectrical differences between sarcopenic and sarcopenic obese men (T2 = 13.4, p < 0.01), mainly due to the higher values of specific R in sarcopenic obese individuals.Conclusion: BIVA detected muscle-mass variations in sarcopenic individuals, and specific BIVA was able to discriminate sarcopenic individuals from sarcopenic obese individuals. These procedures are promising tools for screening for presarcopenia, sarcopenia, and sarcopenic obesity in routine practice.Keywords: aging, body composition, BIVA, DXA

Abstract Background Pancreatic ductal adenocarcinoma (PDAC) remains a leading cause of cancer mortality for which novel gene therapy approaches relying on tumor-tropic adenoviruses are being tested. Methods We obtained the global transcriptional profiling of primary PDAC using RNA from eight xenografted primary PDAC, three primary PDAC bulk tissues, three chronic pancreatitis and three normal pancreatic tissues. The Affymetrix GeneChip HG-U133A was used. The results of the expression profiles were validated applying immunohistochemical and western blot analysis on a set of 34 primary PDAC and 10 established PDAC cell lines. Permissivity to viral vectors used for gene therapy, Adenovirus 5 and Adeno-Associated Viruses 5 and 6, was assessed on PDAC cell lines. Results The analysis of the expression profiles allowed the identification of two clearly distinguishable phenotypes according to the expression of interferon-stimulated genes. The two phenotypes could be readily recognized by immunohistochemical detection of the Myxovirus-resistance A protein, whose expression reflects the activation of interferon dependent pathways. The two molecular phenotypes discovered in primary carcinomas were also observed among established pancreatic adenocarcinoma cell lines, suggesting that these phenotypes are an intrinsic characteristic of cancer cells independent of their interaction with the host's microenvironment. The two pancreatic cancer phenotypes are characterized by different permissivity to viral vectors used for gene therapy, as cell lines expressing interferon stimulated genes resisted to Adenovirus 5 mediated lysis in vitro. Similar results were observed when cells were transduced with Adeno-Associated Viruses 5 and 6. Conclusion Our study identified two molecular phenotypes of pancreatic cancer, characterized by a differential expression of interferon-stimulated genes and easily recognized by the expression of the Myxovirus-resistance A protein. We suggest that the detection of these two phenotypes might help the selection of patients enrolled in virally-mediated gene therapy trials.

Abstract Background The power of haplotype-based methods for association studies, identification of regions under selection, and ancestral inference, is well-established for diploid organisms. For polyploids, however, the difficulty of determining phase has limited such approaches. Polyploidy is common in plants and is also observed in animals. Partial polyploidy is sometimes observed in humans (e.g. trisomy 21; Down's syndrome), and it arises more frequently in some human tissues. Local changes in ploidy, known as copy number variations (CNV), arise throughout the genome. Here we present a method, implemented in the software polyHap, for the inference of haplotype phase and missing observations from polyploid genotypes. PolyHap allows each individual to have a different ploidy, but ploidy cannot vary over the genomic region analysed. It employs a hidden Markov model (HMM) and a sampling algorithm to infer haplotypes jointly in multiple individuals and to obtain a measure of uncertainty in its inferences. Results In the simulation study, we combine real haplotype data to create artificial diploid, triploid, and tetraploid genotypes, and use these to demonstrate that polyHap performs well, in terms of both switch error rate in recovering phase and imputation error rate for missing genotypes. To our knowledge, there is no comparable software for phasing a large, densely genotyped region of chromosome from triploids and tetraploids, while for diploids we found polyHap to be more accurate than fastPhase. We also compare the results of polyHap to SATlotyper on an experimentally haplotyped tetraploid dataset of 12 SNPs, and show that polyHap is more accurate. Conclusion With the availability of large SNP data in polyploids and CNV regions, we believe that polyHap, our proposed method for inferring haplotypic phase from genotype data, will be useful in enabling researchers analysing such data to exploit the power of haplotype-based analyses.

Abstract Background It is well known that different species have different protein domain repertoires, and indeed that some protein domains are kingdom specific. This information has not yet been incorporated into statistical methods for finding domains in sequences of amino acids. Results We show that by incorporating our understanding of the taxonomic distribution of specific protein domains, we can enhance domain recognition in protein sequences. We identify 4447 new instances of Pfam domains in the SP-TREMBL database using this technique, equivalent to the coverage increase given by the last 8.3% of Pfam families and to a 0.7% increase in the number of domain predictions. We use PSI-BLAST to cross-validate our new predictions. We also benchmark our approach using a SCOP test set of proteins of known structure, and demonstrate improvements relative to standard Hidden Markov model techniques. Conclusions Explicitly including knowledge about the taxonomic distribution of protein domains can enhance protein domain recognition. Our method can also incorporate other context-specific domain distributions – such as domain co-occurrence and protein localisation.

IntroductionThrombotic events in neonates and children represent a rare although severe occurrence in view of the associated risk of mortality and sequelae. Quality evidence is limited in this field, and registry studies provide an essential base for research. The aim of this paper is to present the new Italian Registry of Infantile Thrombosis (RITI), set it into the scene of international thrombosis and stroke registries, and provide some insight on the challenges associated with registry management.MethodsWe present the detailed structure and content of the new RITI registry, a brief overview of its main data, and a reflection on its features, pitfalls and the main challenges related to its management.ResultsThe RITI, initially started in 2007 and officially re-launched in 2017 after structural modifications, is a non-interventional retrospective and prospective registry study collecting data on neonatal and pediatric patients (0–18 years) who experienced a systemic or cerebral thrombotic event in Italy. The RITI is managed by a multidisciplinary team with expertise in pediatric thrombosis, and participation is open to all Italian physicians, on a voluntary basis. The overall aim of the registry is to acquire new evidence to better characterize the population of children with thrombotic events and improve their management and outcome. 48 Italian pediatric and intensive care units are actively involved in the RITI, including 85 medical doctors from 16 Italian regions. A total of 1,001 neonates and children affected by cerebral or systemic thrombosis have been enrolled.DiscussionThe RITI is one of the largest available European registries of neonatal and pediatric thrombosis. National registries like the RITI represent a model for the study of rare conditions based on multidisciplinary and multicenter collaboration, aimed at overcoming the limitations due to small populations of patients, and creating a network of experts for patient referral and continuous education. Moreover, registry studies have a pivotal role in the research on pediatric thrombosis, due to the limited feasibility of high-quality studies. In our experience, the main critical stages, pitfalls and challenges in registry management include adequate registry designing, diffusion, data completeness and quality control.

A pea breeding program to increase production in quantity and quality was started in 2005 in the College of Agrarian Sciences (FCA), National University of Rosario (UNR). The first steps were to gather an active collection of germplasm from around the world and to analyze genetic variability through morpho-agronomic and molecular traits in order to set objectives. In 2014, the National Institute of Agropecuarian Technology (INTA) and the FCA-UNR, joined forces to unite inter-institutional efforts for promoting the local development of pea genotypes adapted to the region. This program, using conventional methodologies, has so far obtained a new commercial line (Primogénita FCA-INTA) of green cotyledons, semi-leafless, with high adaptation to local agro ecological conditions and high yield potential. Breeding, nevertheless, is a slow process. Developing new pea varieties usually takes a decade or more when using traditional methodologies; thus, different alternatives were proposed for the reduction of this period. Doubled haploids and in vitro culture have been some of the methodologies developed; in pulses, however, they have not been efficiently implemented in breeding programs. In this context, Speed Breeding emerges as a technology that allows increasing the efficiency of the programs, while reducing costs and the required labor.

Conventional breeding can be complemented by different strategies that increase the efficiency of the methodologies and the current rate of increase in yields in order to meet demand. The use of molecular markers with the aim of developing linkage maps of the species, the use of Blup (Best Linear Unbiased Prediction) for an efficient selection of progenitors to hybridize, the use of in vitro culture to artificially increase the number of F1 plants or the use of digital phenotyping for efficient digital characterization that can be performed during the periodic and routine regeneration of accessions in germplasm collections.

Lentil (Lens culinaris Medik.) is a self-pollinating diploid (2n=2x=14) species belonging to the Fabaceae family. It is one of the oldest crops known, with 8,000 to 9,000 years of history and it is among the earliest domesticates from the Near East Fertile Crescent. The seeds have high nutritional value. This crop is an interesting substitute to wheat in cereal rotations but its importance is low due to a lack of suitable varieties with local adaptation. Some of the major problems that Argentinian lentil breeders face are the narrow genetic base of the current cultivated germplasm and its low yield potential. A lentil breeding program was initiated in 2004 to develop new varieties with adaptation to prevalent conditions in growing areas of Argentina. Germplasm was obtained from ICARDA (International Center for Agricultural Research in the Dry Areas) and local producers. Conventional breeding methods using hybridization and selection are being carried out to develop improved varieties, broad the genetic base, and isolate superior recombinant inbred lines. Two new varieties have been obtained, one of the macrosperm type (Boyerito FCA) and the other of the microsperm type (Tacuarita FCA) through the application of mass selection in F2 populations from the cross of selected materials. This program complements traditional breeding methods with biotechnological techniques such as transgenesis, use of molecular markers, in vitro embryo culture combined with the SSD method to shorten the breeding time, and digital phenotyping.

Aurélie Cointe,1,2 Violaine Walewski,1,3 Claire Amaris Hobson,1 Catherine Doit,1,2 Philippe Bidet,1,2 Laurent Dortet,4–6 Stéphane Bonacorsi,1,2 André Birgy1,2 1IAME, UMR 1137, INSERM, Université Paris Diderot, Sorbonne Paris Cité, AP-HP, Service de Microbiologie, Hôpital Robert-Debré, AP-HP, Paris, France; 2Service de Microbiologie, Centre National de Référence associé Escherichia coli, Hôpital Robert-Debré, AP-HP, Paris, France; 3Service de Microbiologie, Hôpitaux Universitaires de Paris Seine Denis (HUPSSD), site Avicenne, AP-HP, Bobigny, France; 4EA7361, Université Paris-Sud, Université Paris-Saclay, LabEx Lermit, Service de Bactériologie-Hygiène, Hôpital Bicêtre, AP-HP, Le Kremlin-Bicêtre, France; 5Centre National de Référence associé de la résistance aux antibiotiques: Entérobactéries productrices de carbapénémases, Le Kremlin-Bicêtre, France; 6Evolution et Ecologie de la résistance aux antibiotiques, Institut Pasteur - APHP -Université Paris Sud, Paris, FranceCorrespondence: André BirgyService de Microbiologie, Hôpital Robert Debré, 48 Boulevard Serrurier Paris F75019, FranceTel +33140034060Fax +33140032450Email andre.birgy@aphp.frAbstract: The rapid detection of carbapenemase allows implementation of infection control measures and adaptation of antibiotic therapy. We evaluated the performances of the Xpert Carba-R V2® assay for the direct detection and identification of carbapenemase on positive blood cultures. We focused our evaluation on its detection capacity and on the risks of interference due to the patient’s blood. Isolates of several variants of OXA-48-like (n=10), KPC (n=10), NDM (n=11), VIM (n=7), IMP-1 (n=1) carbapenemases and 14 non carbapenemase-producing Enterobacteriaceae were tested. For each isolate (n=53), an aerobic vial was seeded, and incubated in Bactec Fx (Becton Dickinson®) automate. When positive, the Xpert® Carba-R-V2 assay was assessed for carbapenemase detection using 40 μl aliquot. Reproducibility tests were performed on a subset of 23 isolates using aerobic and anaerobic vials. Longer incubation time was also evaluated on 6 isolates. A complementary prospective study in real-time testing of patient-derived clinical samples on 20 additional positive blood vials with Gram negative bacilli on direct examination was performed. Perfect sensitivity and specificity (100%) were observed regardless of the carbapenemase type, the blood vials used and the time of incubation. Xpert® Carba-R-V2 assay is suitable for the rapid detection of the main carbapenemase genes directly on positive blood vials. Its performances and rapid time analysis allow its use in routine to guide therapeutic choices and to implement infection control measures.Keywords: carbapenemase, rapid detection, positive blood culture, GeneXpert, antibiotic therapy, infection control measures

El cáncer infantil es un problema de salud pública en México. Esta enfermedad es motivo de angustia y problemas psicosociales tanto en el paciente como en su cuidador primario. Si las necesidades del cuidador no son identificadas y atendidas se impacta sobre el bienestar y la salud del infante. EI objetivo de la presente investigación fue evaluar las necesidades de apoyo (NA) y calidad de vida del cuidador primario informal (CPI) de pacientes pediátricos con cáncer. Método: El diseño fue no experimental y correlacional. Participaron 100 CPIs de pacientes pediátricos con cáncer hospitalizados, la mayoría fueron mujeres y madres de los pacientes. Resultados: Se encontró que las NA mayormente insatisfechas fueron la necesidad de resolver las preocupaciones por el futuro, seguido por las necesidades emocionales y las necesidades de información. Aquellas percibidas con una menor urgencia por resolver fueron las necesidades relacionadas con el acceso médico de los pacientes. El funcionamiento emocional, físico y social fueron las áreas más afectadas en la calidad de vida (CV). Con respecto al impacto familiar, las relaciones familiares mostraron ser uno de los dominios menos afectados. El análisis de regresión múltiple por método intro demostró que las necesidades emocionales y de información no satisfechas, las preocupaciones, actividades diarias, y relaciones familiares de los CPIs explican el 74% de la varianza en calidad de vida. Conclusión: Se recomienda integrar a su protocolo clínico de rutina la detección de necesidades, evaluación de CV, así como la implementación de intervenciones psicoeducativas y, en su caso, la atención psicológica personalizada.

Frederic Flament,1 Ghislain Francois,1 Huixia Qiu,2 Chengda Ye,2 Tomoo Hanaya,3 Dominique Batisse,3 Suzy Cointereau-Chardon,1 Mirela Donato Gianeti Seixas,4 Susi Elaine Dal Belo,4 Roland Bazin5 1Department of Applied Research and Development, L’Oreal Research and Innovation, Paris, France; 2Department of Applied Research and Development, L’Oreal Research and Innovation, Shanghai, People’s Republic of China; 3Department of Applied Research and Development, L’Oreal Research and Innovation, Tokyo, Japan; 4Department of Applied Research and Development, L’Oreal Research and Innovation, Rio de Janeiro, Brazil; 5RB Consult, Bievres, France Abstract: Skin pores (SP), as they are called by laymen, are common and benign features mostly located on the face (nose, cheeks, etc) that generate many aesthetic concerns or complaints. Despite the prevalence of skin pores, related literature is scarce. With the aim of describing the prevalence of skin pores and anatomic features among ethnic groups, a dermatoscopic instrument, using polarized lighting, coupled to a digital camera recorded the major features of skin pores (size, density, coverage) on the cheeks of 2,585 women in different countries and continents. A detection threshold of 250 µm, correlated to clinical scorings by experts, was input into a specific software to further allow for automatic counting of the SP density (N/cm2) and determination of their respective sizes in mm2. Integrating both criteria also led to establishing the relative part of the skin surface (as a percentage) that is actually covered by SP on cheeks. The results showed that the values of respective sizes, densities, and skin coverage: 1) were recorded in all studied subjects; 2) varied greatly with ethnicity; 3) plateaued with age in most cases; and 4) globally reflected self-assessment by subjects, in particular those who self-declare having “enlarged pores” like Brazilian women. Inversely, Chinese women were clearly distinct from other ethnicities in having very low density and sizes. Analyzing the present results suggests that facial skin pore’s morphology as perceived by human eye less result from functional criteria of associated appendages such as sebaceous glands. To what extent skin pores may be viewed as additional criteria of a photo-altered skin is an issue to be further addressed. Keywords: aging, clinical evaluation, ethnicity, imperfections, oily skin

Abstract Background Malnutrition and sarcopenia significantly increase the risk of intra-hospital delirium, particularly among older adults. Given the potential correlation between calf circumference (CC) and these conditions, CC emerges as a promising predisposing factor for delirium. This study aims to investigate the independent association between delirium and anthropometric parameters, focusing on evaluating CC’s predictive capacity for intra-hospital delirium risk. Additionally, it aims to compare CC’s predictive performance with the widely used Mini Nutritional Assessment (MNA), while also considering potential gender disparities. Methods This is a retrospective study which enrolled patients aged ≥ 65 years from September 2021 to March 2022 at the Padova Hospital (Italy). Physical characteristics, intra-hospital delirium incidence, and body composition were assessed. Sarcopenia was diagnosed using the 2019 European Consensus criteria. Results Among 207 subjects, delirium affected 19% of patients. CC showed a significant association with intra-hospital delirium among the analyzed anthropometric parameters. ROC curves indicated that CC’s predictive capacity for delirium onset was comparable to MNA (p = 0.98), particularly in women. In a multivariable logistic regression model, female gender and higher cognitive and CC scores emerged as protective factors against delirium onset, with each unit increase in CC associated with a 24% reduction in the odds of delirium. Conversely, sarcopenia did not significantly influence delirium onset. Conclusions CC shows promise as a predisposing factor for intra-hospital delirium, similar to MNA, albeit with significant gender differences. CC could serve as a valuable tool for assessing delirium risk among female patients. Further validation of these findings is necessary through larger-scale studies.

Abstract Background Grewia flava infusions are consumed to assist with kidney problems and stomach ailments. However, there are no scientific data on the phytochemical profile or biological properties to validate its folklore use. Thus, the study aimed to assess the phytochemical profile, antioxidant, and antimicrobial activities of Grewia flava twig extracts. Methodology The antioxidant activities of the extracts were assayed using 1,1-diphenyl-2-picrylhydrazyl radical scavenging, reducing power, metal chelation, and total phenolic and flavonoid content assays. The agar well diffusion and microdilution methods were used for crude extracts and fractions (from 80% methanol extract) for antimicrobial screening against P. aeruginosa, S. aureus, E. coli, B. subtilis, A. niger, and R. oryzae. Results The 80% methanol twig extract (250.00 ± 2 GAE/g) exhibited a high concentration of phenolic content, followed by the distilled water extract (192.00 ± 2 mg GAE/g) and the hexane extract (43.10 ± 0.2 mg GAE/g). Fraction 14 of the methanol twig extract exhibited MIC values of 0.21–0.31 mg/mL against all test microorganisms. The root and twig extracts exhibited significant antioxidant and antimicrobial activities, which were attributed to the extracts of bioactive phytochemical compounds such as alkaloids, flavonoids, saponins, steroids, glycosides, anthraquinones, and tannins that were detected in the extracts. Also, the root and twig non-polar extracts were subjected to gas chromatography–mass spectrometry analysis, which identified several bioactive compounds like betulin, β-amyrin, palmitic acid, lupenone, and phytol, highlighting the potential of the plant species as a botanical drug. Conclusions The study supports the traditional use of plant roots and twigs for treating various ailments, indicating their medicinal value. The twigs can be used in place of the roots to guarantee Grewia flava harvesting that is sustainable. However, a comparison of the quantities of the active compound in the twigs and roots using LC–MS is crucial.

Introduction/objectives: Following the IFCC (The International Federation of Clinical Chemistry and Laboratory Medicine) guidelines concerning high-sensitivity cardiac troponin assays, we performed an assessment of the VIDAS® High-Sensitive Troponin I (TNHS) assay. The test was evaluated on its capacity to detect at least 50 % of healthy individuals and checked that the coefficient of variation was less than 10 % at the 99th percentile. Methods: High-sensitivity performance was assessed by examining the limits of detection, the determination of the 99th percentile value, the evaluated imprecision at said value and the detectable results above limit of detection (LoD) in a cohort of healthy European individuals. The capacity of detection on a healthy population of VIDAS® TNHS was validated on a total of 808 plasma samples. Results: One thousand six hundred and nineteen values (888 values for male samples and 731 values for female samples) were included in the analysis. The total imprecision of VIDAS® High-Sensitive Troponin I assay at the 99th percentile was 5.2 %, and 57.4 % of healthy individuals had troponin I values exceeding the LoD. Since the test detected more than 50 % of healthy individuals and had a coefficient of variation less than 10 % at the 99th percentile, it met the criteria of high-sensitivity cardiac troponin assays. Conclusion: VIDAS® High-Sensitive Troponin I assay is a high-sensitivity cardiac troponin assays meeting the definition provided by IFCC guidelines.

Variant calling is fundamental in bacterial genomics, underpinning the identification of disease transmission clusters, the construction of phylogenetic trees, and antimicrobial resistance detection. This study presents a comprehensive benchmarking of variant calling accuracy in bacterial genomes using Oxford Nanopore Technologies (ONT) sequencing data. We evaluated three ONT basecalling models and both simplex (single-strand) and duplex (dual-strand) read types across 14 diverse bacterial species. Our findings reveal that deep learning-based variant callers, particularly Clair3 and DeepVariant, significantly outperform traditional methods and even exceed the accuracy of Illumina sequencing, especially when applied to ONT’s super-high accuracy model. ONT’s superior performance is attributed to its ability to overcome Illumina’s errors, which often arise from difficulties in aligning reads in repetitive and variant-dense genomic regions. Moreover, the use of high-performing variant callers with ONT’s super-high accuracy data mitigates ONT’s traditional errors in homopolymers. We also investigated the impact of read depth on variant calling, demonstrating that 10× depth of ONT super-accuracy data can achieve precision and recall comparable to, or better than, full-depth Illumina sequencing. These results underscore the potential of ONT sequencing, combined with advanced variant calling algorithms, to replace traditional short-read sequencing methods in bacterial genomics, particularly in resource-limited settings.

The inheritance of head color and tightness in globe artichoke was studied utilizing crosses between inbreed lines and between clones and self-pollinated clones from different genetic origins. These genetic materials were sowed in a completely randomized design with 20 plants per plot and genotype. Globe artichoke heads were classified into three colors (purple-green, purple and green) and three head tightness types (compact, fairly compact and soft) and the segregating ratios for these traits tested in each offspring using the chi-square test. Crosses between green and purple inbreed lines produced only purple-green heads but F2 generation segregated at a purple-green:purple:green ratio of 9:3:4. The self-pollinated compact head clones produced a compact head:fairly compact head:soft head ratio of 12:3:1. The remaining crosses between lines and among clones and backcrosses verified these ratios. These results suggest that two loci with a simple recessive epistasis are involved in the inheritance of head color and that two loci with simple dominant epistasis are involved in the expression of the different head tightness types. The inheritance models proposed here could be helpful in predicting the appearance of artichoke heads if breeders need to obtain hybrid seeds for a desirable phenotype.

Objective: Perform the validation and psychometric evaluation of the Brazilian-Portuguese translation of the Functional Outcome of Sleep Questionnaire 10 (FOSQ10). Materials and methods: 182 patients (65 females 48.3 ± 14.4 years and 117 males 46.9 ± 12.4 years), were evaluated by sleep physicians suspected of having Obstructive Sleep Apnea, underwent polysomnography and completed the FOSQ-10 and the Epworth Sleepiness Scale. APA & NCME, 2014 was used to validate the data as the American Educational Research Association recommended. Results: Quality indicators such as Bartlett's test of sphericity (χ2 = 1108.2; gL = 45; p = 0.000010) and KMO (0.83), and adherence measures, attest to the quality of the model. The indicators TLI (0.97), CFI (0.98), and RMSEA (0.04) fall within the expected values. Using the Eigenvalue > 1 technique, two factors explain 53% and 13.3% of the variances. In the Parallel Analysis technique, a single factor explained 59.4653% of the random variance, and the Unidimensionality indicators UniCo = 0.921, ECV = 0.822, and MIREAL = 0.253, were supported. Construct Validity: reliability coefficients Cronbach’s α = 0.87, McDonald’s ordinal Omega index 0.9, and the Composite Reliability 0.891 were satisfactory. Convergent validity: There was a significant Spearman correlation between FOSQ-10 and the Epworth Sleepiness Scale (r = 0.364 [−0.487; −0.226]). Criterion validity: Was not possible to differentiate the groups based on the severity of AHI using FOSQ-10P. Conclusions: The Brazilian translation of FOSQ-10 is valid and reliable for identifying significant effects of excessive daytime sleepiness in patients with Obstructive Sleep Apnea. Level of evidence: 2.

Background and objectives: Anorexia of aging (AoA) is a prevalent geriatric syndrome characterized by a multifactorial decline in appetite and reduced food intake associated with the aging process. This systematic review aims to investigate the use and outcomes of cannabinoids in addressing AoA, with the goal of providing a comprehensive understanding and discussing their potential integration into daily clinical practice. Methods: A thorough search of databases (Embase Ovid, Scopus, PubMed, Cochrane Library, and Web of Science) identified 6100 studies. After eliminating duplicates and screening titles and abstracts, 25 studies underwent full appraisal. Two reviewers assessed inclusion suitability, and study methodologies were evaluated using the Newcastle-Ottawa Scale (NOS) for observational studies and the modified Jadad Scoring Scale for randomized controlled trials. Ultimately, six studies published between 2002 and 2019, involving 869 participants, were included in the review. Results: Out of the 6 fin. l papers selected, 5 were randomized trials, and 1 was a prospective study. Megestrol acetate (800 mg/d) proved to be more effective than dronabinol 2.5 mg twice a day in increasing appetite. Nabilone (at a dosage of 0.5 mg per day) did not show superiority over placebo in alleviating symptoms such as pain, nausea, loss of appetite, and weight. However, with a double dosage followed by 1.0 mg/6 weeks, after eight weeks of treatment, patients recorded a significant increase in calorie intake and carbohydrate consumption compared to the placebo group, with some patients also experiencing substantial weight gain. Regarding delta-9-tetrahydrocannabinol (THC), a weight increase of ≥10% was observed in 17.6% of patients with doses of 5 mg or 10 mg capsules daily, without significant side effects. Additionally, patients treated with THC 2.5 mg reported improved chemosensory perception and increased appetite before meals compared to placebo. No significant side effects were reported in older adults taking cannabinoids. Conclusions: Cannabinoids offer promise in enhancing the quality of life for older individuals with active neoplastic disease. However, to establish comprehensive guidelines, further research with larger sample sizes is essential. Only through this approach can we fully grasp the potential and application of cannabinoids in addressing the nutritional concerns associated with neoplastic diseases.

For over two decades, playwright, screenwriter and film director Martin McDonagh has delighted and shocked audiences around the world with an originality of style and a virulent approach to theatre and film-making. Among several awards, his debut feature film In Bruges (2008) which he wrote and directed, was nominated for a Golden Globe. A self confessed Anglo-Irish artist, McDonagh has amalgamated his Irish background, London upbringing and a particular je ne sais quoi, creating a transnational cinema that reveals a vibrant and enduring migration process. In this paper I will explore the director’s filmic flair, which comprises a self-reflexive style and an incisive application of film text. Despite the dominant hit-man narrative and theme of redemption, I will demonstrate how the two main protagonists in In Bruges inadvertently represent variations of displaced citizens. I will also explore the political incorrectness within the film; how it unveils the tenuousness of patriotism, the predominance of dualistic thought and in doing so ventures towards a reversal of stereotypes. In an exploration of socio-political undercurrents I will also illustrate how the film offers an unenthusiastic appraisal of nationalist ideologies by divulging the inventions of class strictures.

Summary: Continuous assessment of the impact of SARS-CoV-2 on the host at the cell-type level is crucial for understanding key mechanisms involved in host defense responses to viral infection. We investigated host response to ancestral-strain and Alpha-variant SARS-CoV-2 infections within air-liquid-interface human nasal epithelial cells from younger adults (26–32 Y) and older children (12–14 Y) using single-cell RNA-sequencing. Ciliated and secretory-ciliated cells formed the majority of highly infected cell-types, with the latter derived from ciliated lineages. Strong innate immune responses were observed across lowly infected and uninfected bystander cells and heightened in Alpha-infection. Alpha highly infected cells showed increased expression of protein-refolding genes compared with ancestral-strain-infected cells in children. Furthermore, oxidative phosphorylation-related genes were down-regulated in bystander cells versus infected and mock-control cells, underscoring the importance of these biological functions for viral replication. Overall, this study highlights the complexity of cell-type-, age- and viral strain-dependent host epithelial responses to SARS-CoV-2.

Gut microbes are crucial for human health, which are usually accumulated in urban wastewater systems. Seven wastewater treatment plants in Australia with distinct population obesity rates between 18% and 33% were selected for wastewater sampling and analysis. Human gut microbiome were detected using metagenomic sequencing to investigate their associations with the community obesity rate. To unravel this complex relationship, a range of algorithm models, including linear discriminant analysis effect size (LEfSe), similarity percentage analysis (SIMPER), statistical analysis of metagenomic profiles (STAMP), linear models for microarray and RNA-Seq data analysis (LIMMA), Relief, ratio approach for identifying differential abundance (RAIDA), least absolute shrinkage and selection operator (LASSO), support vector machine (SVM), Boruta, DESeq2 and analysis of compositions of microbiomes with bias correction (ANCOM-BC), were used to identify potential bacterial biomarkers for obesity in the wastewater microbiome. Among these algorithm models, LEfSe, LIMMA, SIMPER and SVM are effective in identifying multiple microbial biomarkers. Specific human gut microbes, including Ruminococcus_E, Agathobacter, Fusicatenibacter, Anaerobutyricum, Blautia_A and Neisseria, were identified as potential consensus microbial biomarkers for obesity in the population. A high obesity rate is mainly characterized by a high abundance of pathogenic bacteria and microorganisms associated with xenobiotic biodegradation and metabolism, endocrine and metabolic diseases, and transcription pathways. This study underscores the innovative potential of leveraging human gut microbes in wastewater as biomarkers for monitoring obesity levels across communities, offering a novel, cost-effective, and indirect approach to public health surveillance.

Background: Coronavirus Disease-2019 (COVID-19), driven by the SARS-CoV-2 virus, has disproportionately affected the elderly, with comorbidities like sarcopenia worsening prognosis. Considering the significant impact of RNA vaccines on survival rates in this population, our objective is to investigate the impact of vaccination on the survival of hospitalized elderly patients with COVID-19, considering the presence or absence of sarcopenia. Methods: Prospective study conducted on 159 patients aged>65 years from September 2021 to March 2022. Data about clinical and body composition, and mortality at 12-months after discharge were recorded. Sarcopenia was diagnosed according to the 2019 European Consensus criteria. Results: At the twelfth month post-discharge, vaccinated sarcopenic individuals exhibited a mortality risk similar to vaccinated non-sarcopenic individuals, and lower than unvaccinated non-sarcopenic patients. Cox regression analysis, adjusted for age, gender, comorbidity, functional and vaccinal status, showed that the presence of sarcopenia did not significantly impact the risk of death within 12-months post-discharge. Discussion: Vaccination emerges as a protective measure for sarcopenic patients, countering the potential adverse effects of sarcopenia on COVID-19 outcomes, underscoring the importance of immunization in the frail elderly with a call for meticulous monitoring of its benefits. Conclusions: Our study represents the first attempt to analyze the vaccine's effect on survival in sarcopenic hospitalized older adults with COVID-19. The administration of vaccination to sarcopenic patients proves pivotal, as its omission could lead to notably unfavorable outcomes within this specific population.

ABSTRACTWe aimed to evaluate the performance of Oxford Nanopore Technologies (ONT) sequencing from positive blood culture (BC) broths for bacterial identification and antimicrobial susceptibility prediction. Patients with suspected sepsis in four intensive care units were prospectively enrolled. Human-depleted DNA was extracted from positive BC broths and sequenced using ONT (MinION). Species abundance was estimated using Kraken2, and a cloud-based system (AREScloud) provided in silico predictive antimicrobial susceptibility testing (AST) from assembled contigs. Results were compared to conventional identification and phenotypic AST. Species-level agreement between conventional methods and AST predicted from sequencing was 94.2% (49/52), increasing to 100% in monomicrobial infections. In 262 high-quality AREScloud AST predictions across 24 samples, categorical agreement (CA) was 89.3%, with major error (ME) and very major error (VME) rates of 10.5% and 12.1%, respectively. Over 90% CA was achieved for some taxa (e.g., Staphylococcus aureus) but was suboptimal for Pseudomonas aeruginosa. In 470 AST predictions across 42 samples, with both high quality and exploratory-only predictions, overall CA, ME, and VME rates were 87.7%, 8.3%, and 28.4%. VME rates were inflated by false susceptibility calls in a small number of species/antibiotic combinations with few representative resistant isolates. Time to reporting from sequencing could be achieved within 8–16 h from BC positivity. Direct sequencing from positive BC broths is feasible and can provide accurate predictive AST for some species. ONT-based approaches may be faster but significant improvements in accuracy are required before it can be considered for clinical use.IMPORTANCESepsis and bloodstream infections carry a high risk of morbidity and mortality. Rapid identification and susceptibility prediction of causative pathogens, using Nanopore sequencing direct from blood cultures, may offer clinical benefit. We assessed this approach in comparison to conventional phenotypic methods and determined the accuracy of species identification and susceptibility prediction from genomic data. While this workflow holds promise, and performed well for some common bacterial species, improvements in sequencing accuracy and more robust predictive algorithms across a diverse range of organisms are required before this can be considered for clinical use. However, results could be achieved in timeframes that are faster than conventional phenotypic methods.

Abstract Background Although the management of sarcoma is improving, non adherence to clinical practice guidelines (CPGs) remains high, mainly because of the low incidence of the disease and the variety of histological subtypes. Since little is known about the health economics of sarcoma, we undertook a cost-effectiveness analysis (within the CONnective TIssue CAncer NETwork, CONTICANET) comparing costs and outcomes when clinicians adhered to CPGs and when they did not. Methods Patients studied had a histological diagnosis of sarcoma, were older than 15 years, and had been treated in the Rhône-Alpes region of France (in 2005/2006) or in the Veneto region of Italy (in 2007). Data collected retrospectively for the three years after diagnosis were used to determine relapse free survival and health costs (adopting the hospital's perspective and a microcosting approach). All costs were expressed in euros (€) at their 2009 value. A 4% annual discount rate was applied to both costs and effects. The incremental cost-effectiveness ratio (ICER) was expressed as cost per relapse-free year gained when management was compliant with CPGs compared with when it was not. To capture uncertainty surrounding ICER, a probabilistic sensitivity analysis was performed based on a non-parametric bootstrap method. Results A total of 219 patients were included in the study. Compliance with CPGs was observed for 118 patients (54%). Average total costs reached 23,571 euros when treatment was in accordance with CPGs and 27,313 euros when it was not. In relation to relapse-free survival, compliance with CPGs strictly dominates non compliance, i.e. it is both less costly and more effective. Taking uncertainty into account, the probability that compliance with CPGs still strictly dominates was 75%. Conclusions Our findings should encourage physicians to increase their compliance with CPGs and healthcare administrators to invest in the implementation of CPGs in the management of sarcoma.

Bovine respiratory disease (BRD) is the leading cause of morbidity and mortality in feedlot cattle. Bovine herpesvirus-1 (BHV-1) is one of the main culprits of BRD; however, research on BHV-1 is hampered by the lack of suitable models for infection and drug testing. In this study, we established a novel bovine tracheal organoid culture grown in a basement membrane extract type 2 (BME2) matrix and compared it with the air–liquid interface (ALI) culture system. After differentiation, the matrix-embedded organoids developed beating cilia and demonstrated a transcriptomic profile similar to the ALI culture system. The matrix-embedded organoids were also highly susceptible to BHV-1 infection and immune stimulation by Pam2Cys, an immunomodulator, which resulted in robust cytokine production and tracheal antimicrobial peptide mRNA upregulation. However, treatment of bovine tracheal organoid cultures with Pam2Cys was not sufficient to inhibit viral infection or replication, suggesting a role of the non-epithelial cellular microenvironment in vivo.

A pesquisa monitorou menções aos termos “fake news”, “verdade” e “mentira” nas publicações dos candidatos Lula e Bolsonaro em seus perfis no Twitter durante a campanha eleitoral para presidente do Brasil em 2022, com o objetivo de compreender os sentidos produzidos no discurso dos candidatos, seguindo a metodologia de Análise de Discurso de linha francesa. Parte-se de estudos contemporâneos sobre desinformação nas plataformas digitais para a problematização teórica dos conceitos. Como resultados, temos uma postura retórica nas postagens de Jair Bolsonaro, no intuito de reforçar uma visão particular de “verdade” e “mentira” - não foram encontradas citações ao termo “fake news” -, enquanto Lula busca confirmar a veracidade de suas declarações ou reiterar a falsidade do que diz o adversário, utilizando técnicas discursivas similares às de verificadores profissionais, concentrando todas as citações à expressão “fake news” no corpus da pesquisa.

Zaccaria e Balestra hanno presentato un caso che pone al centro dell’attenzione il tema del conflitto e della sua gestione all’interno di una terapia di coppia. Lo fanno con riferimento all’approccio sistemico, ma mettendo in evidenza alcuni aspetti che possiamo ritenere comuni ai differenti modelli di intervento con la coppia. Partirei proprio da questi ultimi, quali ambiti di interesse trasversale, per poi proporre una riflessione sul conflitto di coppia nella prospettiva di Psicoanalisi della Relazione. [...]

Summary: Super-enhancers (SEs) are stretches of enhancers ensuring a high level of expression of key genes associated with cell function. The identification of cancer-specific SE-driven genes is a powerful means for the development of innovative therapeutic strategies. Here, we identify a MITF/SOX10/TFIIH-dependent SE promoting the expression of BAHCC1 in a broad panel of melanoma cells. BAHCC1 is highly expressed in metastatic melanoma and is required for tumor engraftment, growth, and dissemination. Integrative genomics analyses reveal that BAHCC1 is a transcriptional regulator controlling expression of E2F/KLF-dependent cell-cycle and DNA-repair genes. BAHCC1 associates with BRG1-containing remodeling complexes at the promoters of these genes. BAHCC1 silencing leads to decreased cell proliferation and delayed DNA repair. Consequently, BAHCC1 deficiency cooperates with PARP inhibition to induce melanoma cell death. Our study identifies BAHCC1 as an SE-driven gene expressed in melanoma and demonstrates how its inhibition can be exploited as a therapeutic target.

The conformation of GPCR-arrestin complexes at the cell membrane, despite available structures, remains uncertain. This work reveals structure and dynamics of the PTH1R-arrestin2 complex, including flexible regions, in live cells.

A variant of group A Streptococcus serotype M1 (UK) has been increasingly reported and can be differentiated from the global variant by its overexpression of the superantigen SpeA. Here, Davies et al probe the mechanism behind enhanced SpeA expression and demonstrate that a SNP in the 5’ leader sequence of ssrA is responsible for this virulence phenotype.

Here the authors show that the exonuclease EXD2 is involved in the recovery of class II gene transcription after UV irradiation. EXD2 travels from the mitochondria to the nucleus to interact with RNA Pol II and degrade new synthetized mRNA to allow transcription following DNA repair.

Background Some studies show an association between the apolipoprotein E ε4 allele (ApoEε4) and obstructive sleep apnea syndrome (OSAS), and other studies, an association between ApoEε4 and excessive daytime sleepiness (EDS), but there are no data in the literature on the interaction between EDS, cognitive function, and ApoEε4 in patients with OSA. Objective To examine the cognitive function of adults with and without EDS and with and without ApoEε4. Methods A total of 21 male and female patients aged between 33 and 79 years, underwent a clinical interview, ApoE genotyping, neuropsychological evaluation, polysomnography, and the application of the Epworth Sleepiness Scale. Results Excessive daytime sleepiness was associated with lower intelligence quotient (IQ; total performance) and worse immediate visual memory, regardless of the ApoE genotype. Patients carrying the ApoEε3/ε4 genotype had a worse performance in divided attention, constructional praxis, perceptual organization, and cognitive flexibility. A combination of the ε4 allele and EDS potentiates the negative effect on cognition, except for immediate visual memory. In this case, patients had a worse performance in terms of processing speed, selective attention, and visuomotor coordination. Conclusions Excessive daytime sleepiness and the ApoEε3/ε4 genotype are associated with worse cognitive performance in OSA patients. The combination of EDS and ε4 allele potentiates cognitive impairment.

Summary: Background: The PERFORM study aimed to understand causes of febrile childhood illness by comparing molecular pathogen detection with current clinical practice. Methods: Febrile children and controls were recruited on presentation to hospital in 9 European countries 2016–2020. Each child was assigned a standardized diagnostic category based on retrospective review of local clinical and microbiological data. Subsequently, centralised molecular tests (CMTs) for 19 respiratory and 27 blood pathogens were performed. Findings: Of 4611 febrile children, 643 (14%) were classified as definite bacterial infection (DB), 491 (11%) as definite viral infection (DV), and 3477 (75%) had uncertain aetiology. 1061 controls without infection were recruited. CMTs detected blood bacteria more frequently in DB than DV cases for N. meningitidis (OR: 3.37, 95% CI: 1.92–5.99), S. pneumoniae (OR: 3.89, 95% CI: 2.07–7.59), Group A streptococcus (OR 2.73, 95% CI 1.13–6.09) and E. coli (OR 2.7, 95% CI 1.02–6.71). Respiratory viruses were more common in febrile children than controls, but only influenza A (OR 0.24, 95% CI 0.11–0.46), influenza B (OR 0.12, 95% CI 0.02–0.37) and RSV (OR 0.16, 95% CI: 0.06–0.36) were less common in DB than DV cases. Of 16 blood viruses, enterovirus (OR 0.43, 95% CI 0.23–0.72) and EBV (OR 0.71, 95% CI 0.56–0.90) were detected less often in DB than DV cases. Combined local diagnostics and CMTs respectively detected blood viruses and respiratory viruses in 360 (56%) and 161 (25%) of DB cases, and virus detection ruled-out bacterial infection poorly, with predictive values of 0.64 and 0.68 respectively. Interpretation: Most febrile children cannot be conclusively defined as having bacterial or viral infection when molecular tests supplement conventional approaches. Viruses are detected in most patients with bacterial infections, and the clinical value of individual pathogen detection in determining treatment is low. New approaches are needed to help determine which febrile children require antibiotics. Funding: EU Horizon 2020 grant 668303.

La Didattica Enattiva pone il suo punto di forza nella partecipazione di tutti all'attività didattica, nella co-costruzione di un sapere che unisce cognizioni, azioni ed emozioni, attraverso dialogo ed esperienza condivisa. Proprio in funzione di questa circolarità di feedback e della ricchezza del vissuto personale, la valutazione risulta essere un punto dolente dell'approccio. La Ricerca Partecipata, mostrando numerosi punti in comune con esso, si presta come metodologia di analisi che apporta un substrato teorico e strumentale più solido alla questione valutativa. Viene qui riportato un esempio di lezione, in cui alcune tecniche di ricerca partecipata vengono applicate durante lo svolgimento di attività di Pensiero Contemplativo. Lo scopo è quello di incentivare il dialogo, la conoscenza reciproca tra compagni di classe, nonché l’esplicitazione di conoscenze e vissuti personali legati alla tematica disciplinare trattata, per una visione valutativa più completa. I risultati hanno suscitato l’interesse degli studenti e delle docenti.

ABSTRACT Background Obstructive sleep apnea syndrome (OSAS) is characterized by episodes of upper airway obstruction during sleep, with a risk of cardiovascular and cerebrovascular diseases. There is no tool in Brazil to measure the impact of treatment on patients with OSAS. Objective To translate and culturally adapt the Sleep Apnea Quality of Life Index (SAQLI) into Brazilian Portuguese. Methods The translation and cultural adaptation were carried out in five steps: translation, synthesis of the translations, back translation, review committee and pretesting. Results A version of a culturally compatible SAQLI was constructed after lexical changes, along with changes to the sentence structures, visual format, instructions and cards. The essence of the questionnaire and its social, emotional, and disease impact in treatment measures was maintained, with 80% understanding. Conclusions The questionnaire was translated and adapted culturally to Brazilian Portuguese, and presented good comprehension in the study population.

BackgroundNumerous individual and organizational factors can influence the spread of SARS-CoV-2 infection in Long Term Care Facilities (LTCFs). A range of outbreak control measures are still implemented in most facilities involving administrations, staff, residents and their families. This study aims to evaluate which measure could influence the transmission of SARS-CoV-2 infection among residents during the period March 2021-June 2022.MethodsWe enrolled 3,272 residents aged ≥60 years. The outbreak control measures adopted to prevent or manage the infection included entry regulations, contact-regulating procedures, and virological surveillance of residents and staff. The association between LTCFs' and participants' characteristics with new cases of COVID-19 infections was analyzed using multilevel logistic regression models.ResultsIn 33.8% of the facilities 261 cases of SARS-CoV-2 infection were reported. Among participant characteristics, gender and age were not associated with SARS-CoV-2 infection, while having received the vaccine booster dose was protective against infection [Odds Ratio (OR) = 0.34, 95% Confidence Interval (CI) 0.12–0.99, p = 0.048]. In addition, the implementation of protected areas for family visits was associated with a significant reduction of the probability of infections (OR = 0.18, 95% CI 0.03–0.98, p = 0.047). Overall, about 66% of the variability in the probability of SARS-CoV-2 infection during the observational period may be due to facility structure characteristics and 34% to the participant characteristics.ConclusionsThese data showed that vaccination booster doses and family visit restriction-control are still needed to make the LTCFs safer against SARS-CoV-2 infection.

Abstract Background Molecular mechanisms determining the transmission and prevalence of drug resistant tuberculosis (DR-TB) in Papua New Guinea (PNG) are poorly understood. We used genomic and drug susceptibility data to explore the evolutionary history, temporal acquisition of resistance and transmission dynamics of DR-TB across PNG. Methods We performed whole genome sequencing on isolates from Central Public Health Laboratory, PNG, collected 2017–2019. Data analysis was done on a composite dataset that also included 100 genomes previously sequenced from Daru, PNG (2012–2015). Results Sampled isolates represented 14 of the 22 PNG provinces, the majority (66/94; 70%) came from the National Capital District (NCD). In the composite dataset, 91% of strains were Beijing 2.2.1.1, identified in 13 provinces. Phylogenetic tree of Beijing strains revealed two clades, Daru dominant clade (A) and NCD dominant clade (B). Multi-drug resistance (MDR) was repeatedly and independently acquired, with the first MDR cases in both clades noted to have emerged in the early 1990s, while fluoroquinolone resistance emerged in 2009 (95% highest posterior density 2000–2016). We identified the presence of a frameshift mutation within Rv0678 (p.Asp47fs) which has been suggested to confer resistance to bedaquiline, despite no known exposure to the drug. Overall genomic clustering was significantly associated with rpoC compensatory and inhA promoter mutations (p

Abstract Background In older and multimorbid patients, chronic conditions may affect the prognostic validity of computed tomography (CT) findings in COVID-19. This study aims at assessing to which extent CT findings have prognostic implications in COVID-19 older patients. Methods Hospitalized COVID-19 patients aged 60 years or more enrolled in the multicenter, observational and longitudinal GeroCovid study who underwent chest CT were included. Patients were stratified by tertiles of age and pneumonia severity to compare CT findings. Hierarchical clustering based on CT findings was performed to identify CT-related classificatory constructs, if any. The hazard ratio (HR) of mortality was calculated for individual CT findings and for clusters, after adjusting for potential confounders. Results 380 hospitalized COVID-19 patients, with a mean age of 78 (SD:9) years, underwent chest CT scan. Ground glass opacity (GGO), consolidation, and pleural effusion were the three most common CT findings, with GGO prevalence decreasing from younger to older patients and pleural effusion increasing. More severe the pneumonia more prevalent were GGO, consolidation and pleural effusion. HR of mortality was 1.94 (95%CI 1.24–3.06) for pleural effusion and 13 (95%CI 6.41–27) for cluster with a low prevalence of GGO and a high prevalence of pleural effusion (“LH”), respectively. Out of the three CT based clusters, “LH” was the only independent predictor in the multivariable model. Conclusions Pleural effusion qualifies as a distinctive prognostic marker in older COVID-19 patients. Research is needed to verify whether pleural effusion reflects COVID-19 severity or a coexisting chronic condition making the patient at special risk of death. Trial registration ClinicalTrials.gov: NCT04379440

Abstract Small‐Cell Lung Cancer (SCLC) is an aggressive neuroendocrine malignancy with a poor prognosis. Here, we focus on the neuroendocrine SCLC subtypes, SCLC‐A and SCLC‐N, whose transcription addiction was driven by ASCL1 and NEUROD1 transcription factors which target E‐box motifs to activate up to 40% of total genes, the promoters of which are maintained in a steadily open chromatin environment according to ATAC and H3K27Ac signatures. This leverage is used by the marine agent lurbinectedin, which preferentially targets the CpG islands located downstream of the transcription start site, thus arresting elongating RNAPII and promoting its degradation. This abrogates the expression of ASCL1 and NEUROD1 and of their dependent genes, such as BCL2, INSM1, MYC, and AURKA, which are responsible for relevant SCLC tumorigenic properties such as inhibition of apoptosis and cell survival, as well as for a part of its neuroendocrine features. In summary, we show how the transcription addiction of these cells becomes their Achilles’s heel, and how this is effectively exploited by lurbinectedin as a novel SCLC therapeutic endeavor.

Abstract Background Circulating cell-free DNA (cfDNA) in the plasma of cancer patients contains cell-free tumour DNA (ctDNA) derived from tumour cells and it has been widely recognized as a non-invasive source of tumour DNA for diagnosis and prognosis of cancer. Molecular profiling of ctDNA is often performed using targeted sequencing or low-coverage whole genome sequencing (WGS) to identify tumour specific somatic mutations or somatic copy number aberrations (sCNAs). However, these approaches cannot efficiently detect all tumour-derived genomic changes in ctDNA. Methods We performed WGS analysis of cfDNA from 4 breast cancer patients and 2 patients with benign tumours. We sequenced matched germline DNA for all 6 patients and tumour samples from the breast cancer patients. All samples were sequenced on Illumina HiSeqXTen sequencing platform and achieved approximately 30x, 60x and 100x coverage on germline, tumour and plasma DNA samples, respectively. Results The mutational burden of the plasma samples (1.44 somatic mutations/Mb of genome) was higher than the matched tumour samples. However, 90% of high confidence somatic cfDNA variants were not detected in matched tumour samples and were found to comprise two background plasma mutational signatures. In contrast, cfDNA from the di-nucleosome fraction (300 bp–350 bp) had much higher proportion (30%) of variants shared with tumour. Despite high coverage sequencing we were unable to detect sCNAs in plasma samples. Conclusions Deep sequencing analysis of plasma samples revealed higher fraction of unique somatic mutations in plasma samples, which were not detected in matched tumour samples. Sequencing of di-nucleosome bound cfDNA fragments may increase recovery of tumour mutations from plasma.

Mycobacterium tuberculosis genome comprises approximately 10% of two families of poorly characterised genes due to their high GC content and highly repetitive nature. The largest sub-group, the proline-glutamic acid polymorphic guanine-cytosine-rich sequence (PE_PGRS) family, is thought to be involved in host response and disease pathogenicity. Due to their high genetic variability and complexity of analysis, they are typically disregarded for further research in genomic studies. There are currently limited online resources and homology computational tools that can identify and analyse PE_PGRS proteins. In addition, they are computational-intensive and time-consuming, and lack sensitivity. Therefore, computational methods that can rapidly and accurately identify PE_PGRS proteins are valuable to facilitate the functional elucidation of the PE_PGRS family proteins. In this study, we developed the first machine learning-based bioinformatics approach, termed PEPPER, to allow users to identify PE_PGRS proteins rapidly and accurately. PEPPER was built upon a comprehensive evaluation of 13 popular machine learning algorithms with various sequence and physicochemical features. Empirical studies demonstrated that PEPPER achieved significantly better performance than alignment-based approaches, BLASTP and PHMMER, in both prediction accuracy and speed. PEPPER is anticipated to facilitate community-wide efforts to conduct high-throughput identification and analysis of PE_PGRS proteins.