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Simple Summary: Hepatocellular carcinoma (HCC) is a leading cause of cancer deaths globally. Current gold-standard screening methods include imaging every six months and measuring alpha-fetoprotein (AFP) levels. This study evaluates Protein Induced by Vitamin K Absence-II (PIVKA-II) as a diagnostic biomarker for HCC and its correlation with disease stage. PIVKA-II levels progressively increase from chronic hepatitis C to liver cirrhosis and are highest in HCC patients, with levels correlating to advanced HCC stages based on the Barcelona Clinic Liver Cancer system. The optimal PIVKA-II threshold (>37 mAU/mL) achieved 80% sensitivity and 76% specificity, outperforming AFP, which had 53% specificity and 78% sensitivity at a cut-off of 5.2 ng/mL. Combining PIVKA-II and AFP improved diagnostic accuracy, achieving a positive predictive value of 73.9% and a negative predictive value of 94.2%. The findings suggest that PIVKA-II performs better than AFP alone and that their combined use enhances diagnostic accuracy, especially for advanced disease stages. Background and Aims: Hepatocellular carcinoma (HCC) represents the second leading cause of cancer deaths worldwide. Six-month imaging along with alpha-fetoprotein (AFP) serum levels detection are the current gold standard to exclude HCC. Protein induced by vitamin K absence (PIVKA-II) has been proposed as a potential screening biomarker for HCC. This study was designed to evaluate the role of PIVKA-II as diagnostic HCC marker, and the correlation between PIVKA-II levels and HCC stage. Methods: PIVKA-II levels were assessed on serum samples of Italian patients. The study population included 80 patients with HCC, 111 with liver cirrhosis (LC), and 111 with chronic hepatitis C (CHC). Results: PIVKA-II serum levels progressively increase from patients with CHC to patients with HCC. In the HCC group, PIVKA-II values are higher in the more advanced stages of the disease, assessed by the Barcelona Clinic Liver Cancer (BCLC) staging system (BCLC-B vs. BCLC-A vs. BCLC-0). Youden's index analysis identified a value >37 mAU/mL as the optimal threshold for the best combination of sensitivity and specificity (80% and 76%, respectively) and, at the best cut-off of 5.2 ng/mL, AFP yielded 53% specificity and 78% sensitivity. The combination of PIVKA-II and AFP reached positive and negative predictive values of 73.9% and 94.2%, respectively. Conclusions: PIVKA-II levels are increased in the HCC patients, compared to control groups. The increase is more evident in patients with advanced HCC. The diagnostic performance of PIVKA-II seems more sensitive than AFP while the combination of PIVKA-II and AFP resulted in the best diagnostic accuracy, reaching 73.9% positive predictive value and 94.2% negative predictive value, thus improving the diagnostic capability of the single marker. [ABSTRACT FROM AUTHOR]

Background: Hand eczema (HE) is a common skin disease with a negative impact on patients' quality of life in occupational and non‐occupational settings. Up‐to‐date, data on HE in Italian patients referred for patch testing are lacking. Objectives: To characterise the profile in terms of demographics, aetiology and patch test results of Italian patients affected by HE referred for patch testing. Methods: A retrospective descriptive study on consecutive patients affected by HE who underwent patch testing from 2016 to 2023 in eight dermatology clinics was performed. HE patients were divided into two groups according to the exclusive (HE‐only group) and not‐exclusive (HE+ group) hand involvement, and compared to patients with eczema localised in body areas other than hands (NHE group). Results: One thousand five hundred and ninety‐seven patients were affected by HE (35.3% males; mean age 42.7 years), 60.2% belonging to the HE‐only group and 39.8% to the HE+ group. Occupational dermatitis was diagnosed in 33.2% of HE‐only patients, 25.0% of HE+ patients and 5.2% of NHE patients (p < 0.001). HE‐only patients presented: Allergic Contact Dermatitis (ACD), Irritant Contact Dermatitis (ICD), atopic HE in 48.1%, 47.5% and 7.1%, respectively; hyperkeratotic palmar, acute recurrent vesicular and nummular clinical subtypes in 52.2%, 43.9% and 11.9%, respectively; relevant positive patch test reactions in 48.1% (nickel sulphate 18.9%, methylchloroisothiazolinone/methylisothiazolinone 10.6%, methylisothiazolinone 8.6%, p‐phenylenediamine 6.0% and potassium dichromate 4.7%). Conclusions: HE patients, and particularly those with exclusive hand involvement, show a particular profile in terms of demographic and clinical characteristics, etiologies and relevant positive patch test reactions. [ABSTRACT FROM AUTHOR]

Optimising antimicrobial usage (AMU) in livestock is pivotal to counteract the emergence of antimicrobial resistance. We analysed AMU in more than 1000 cattle herds over 11 years (2008–2018) in the Aosta Valley (Italy), a region where 80% of farms house less than 50 cattle. Dairy cows accounted for over 95% of AMU. AMU was estimated using the defined daily dose animal for Italy (DDDAit) per biomass for the whole herd and a treatment incidence 100 (TI100) for cows. Average annual herd-level AMU was low, with 3.6 DDDAit/biomass (range: 3.2–4.0) and 1.2 TI100 in cows (range: 1.1–1.3). Third and fourth generation cephalosporins, which are critical for human medicine, represented almost 10% of usage, and intramammary antimicrobials accounted for over 60%. We detected significant downward temporal trends in total AMU, as well as a positive relationship with herd size. The magnitude of such effects was small, leaving scant room for further reduction. However, the frequent use of critical antimicrobials and intramammary products should be addressed, following the principles of prudent AMU. Our findings highlight the importance of monitoring AMU even in low-production, smallholding contexts where a low usage is expected, to identify any deficiencies and implement interventions for further AMU optimisation.

In the past, high- z active galactic nuclei (AGNs) were given a minor role as possible drivers of reionization, despite initial evidence in favor of their large space densities at low luminosities by Chandra and the Hubble Space Telescope. Recent observations from JWST are finding relatively large numbers of faint AGNs at z > 4, convincingly confirming these early results. We present a sample of z ∼ 5 AGNs, both from wide, shallow ground-based surveys and from deep, pencil-beam observations from JWST, allowing us to estimate their space densities with unprecedented accuracy. The bright end ( M _1450 < −26) of the z ∼ 5 AGN luminosity function is well constrained, with a rather steep slope. The faint end ( M _1450 ≥ −22) indicates a high space density, the scatter is significant, and the knee ( M _1450 ∼ −24) is mostly undetermined. Comparisons with state-of-the-art models find reasonable agreement with the observed AGN luminosity function at z = 5, while the predicted space density evolution at higher redshifts appears to be too fast with respect to observational constraints. Given the large variance at the faint end, we consider different options in fitting the luminosity functions and deriving the ionizing emissivity. Even in the most conservative scenario, the photoionization rate produced by z ∼ 5 AGNs is consistent with the ultraviolet background measurements. A slow evolution of the space density of faint AGNs is observed, indicating that active SMBHs are probably producing large amounts of ionizing photons at z > 6, well into the Epoch of Reionization. This is an important indication that high- z AGNs could be major contributors to the reionization of the Universe.

Abstract Little is known about how co-infections and genotype dynamics affect Mycoplasma hyopneumoniae infection in fattening pigs. This study was aimed at assessing the role of co-infections in M. hyopneumoniae outbreaks, their influence on the presence of M. hyopneumoniae genotypes and their impact on consequent lung lesions. Tracheobronchial swabs (TBS) from 300 finishers were collected from 10 farms at the onset of enzootic pneumonia outbreaks and 1 month later, sampling of 3 groups per farm: Group A showed clinical signs first, Group B was housed near Group A, and Group C was located in a different building. Pigs’ lungs were scored at the slaughterhouse. TBS were tested for the main pathogens involved in respiratory diseases, and samples positive for M. hyopneumoniae were genotyped by multiple-locus variable-number tandem repeat analysis (MLVA). Pigs in Group A showed the highest prevalence and load of M. hyopneumoniae. A positive association was detected between M. hyopneumoniae and Mycoplasma hyorhinis, whereas Actinobacillus pleuropneumoniae was more frequent when the M. hyopneumoniae load was higher. Nevertheless, co-infection had no effect on lung lesion scores. The presence of multiple MLVA types (mixed infections) increased in time only in pigs from Group C and was positively associated with porcine reproductive and respiratory syndrome virus infection. Lung lesions were more severe in pigs with at least one TBS positive for M. hyopneumoniae and in pigs with a history of mixed infections. The central role of M. hyopneumoniae and relevance of mixed infections suggest that increased biosecurity might be beneficial for lung lesion sequelae.

This study was carried out within the project “Roma Hispana. Nuevas tecnologías aplicadas al estudio histórico, la musealización y la puesta en valor de Patrimonio Cultural español en Roma: la spezieria di Santa Maria della Scala” (Universitat de València Spain), which is funded by the Conselleria d’Innovació, Universitats, Ciència i Societat Digital of the Generalitat Valenciana (2020–2021) and authorized by the Sovrintendenza Speciale Archeologia Belle Arti e Paesaggio (Special Superintendence of Archeology, Fine Arts and Landscape) of Rome, Italy. The spezieria di Santa Maria della Scala was the oldest apothecary in Europe managed by the order of Discalced Carmelite friars. Operating between the second half of the seventeenth century and the mid-twentieth century, over time it acquired great prestige, becoming known as the Pharmacy of the Popes. The aims of the “Roma Hispana” project are to study, musealize and disseminate the material and immaterial cultural heritage of this historical spezieria by combining physicochemical and cultural studies, new 3D technologies, and artificial intelligence. As a case study, in this paper we report the application of a laser scanner prototype for 3D color imaging of the spezieria’s sales room and use a simpler photogrammetry method to collect analogous data in the small nearby storeroom coupled to the high-power capabilities of the ENEA parallel computer facility. Digital data were collected to enable a virtual tour that provides a fully navigable, faithful, high-resolution 3D color model to render this ancient Roman apothecary accessible and usable to interested members of the public and experts in the sector (art historians, restorers, etc.). We also describe the 3D technology used to obtain three-dimensional images of the cultural assets of these spaces (mostly drug containers) and its results. The ultimate aim of this study is to achieve the virtual musealization of the heritage complex.

Abstract There is growing interest on the potential clinical relevance of the endometrial microbiome. However, insufficient attention has been given to the methodology of sampling. To minimize contamination, we advocate the use of the double-lumen catheters commonly employed for the embryo transfer. Endometrial fluid samples obtained from 53 women scheduled for IVF were studied for microbiome characterization. Control samples from the vagina of these same women were concomitantly obtained. Samples were analysed by V3–V4–V6 regions of 16S rRNA gene sequencing with Next Generation Sequencing technique. Endometrial Lactobacillus-dominant cases were uncommon compared to previous evidence, being observed in only 4 (8%) women. Taxonomy markedly differed between the endometrial and vaginal microbiomes composition. The most common bacterial genera coincided in only 4 (8%) women. The comparison between women who did and did not subsequently become pregnant failed to identify any microorganism associated with the success of the procedure. However, the endometrial biodiversity resulted higher among pregnant women. Shannon’s Equitability index in pregnant and non pregnant women was 0.76 [0.57–0.87] and 0.55 [0.51–0.64], respectively (p = 0.002). In conclusion, the use of embryo transfer catheters for testing the endometrial microbiome is promising. The scant concordance with vaginal samples supports the validity of this approach. Moreover, our study highlighted a possible beneficial role of a higher biodiversity on endometrial receptivity.

Abstract Approximately a half of breast tumors classified as HER2-negative exhibit HER2-low-positive expression. We recently described a high instability of HER2-low-positive expression from primary breast cancer (BC) to relapse. Previous studies reporting discordance in HER2 status between baseline biopsy and residual disease (RD) in patients undergoing neoadjuvant treatment did not include the HER2-low-positive category. The aim of this study is to track the evolution of HER2-low-positive expression from primary BC to RD after neoadjuvant treatment. Patients undergoing neoadjuvant treatment with available baseline tumor tissue and matched samples of RD (in case of no pCR) were included. HER2-negative cases were sub-classified as HER2-0 or HER2-low-positive (IHC 1+ or 2+ and ISH negative). Four-hundred forty-six patients were included. Primary BC phenotype was: HR-positive/HER2-negative 23.5%, triple-negative (TN) 35%, HER2-positive 41.5%. HER2-low-positive cases were 55.6% of the HER2-negative cohort and were significantly enriched in the HR-positive/HER2-negative vs. TN subgroup (68.6% vs. 46.8%, p = 0.001 χ 2 test). In all, 35.3% of non-pCR patients (n = 291) had a HER2-low-positive expression on RD. The overall rate of HER2 expression discordance was 26.4%, mostly driven by HER2-negative cases converting either from (14.8%) or to (8.9%) HER2-low-positive phenotype. Among HR-positive/HER2-negative patients with HER2-low-positive expression on RD, 32.0% and 57.1% had an estimated high risk of relapse according to the residual proliferative cancer burden and CPS-EG score, respectively. In conclusion, HER2-low-positive expression showed high instability from primary BC to RD after neoadjuvant treatment. HER2-low-positive expression on RD may guide personalized adjuvant treatment for high-risk patients in the context of clinical trials with novel anti-HER2 antibody-drug conjugates.

Abstract The aims of this study were to characterize new SARS-CoV-2 genomes sampled all over Italy and to reconstruct the origin and the evolutionary dynamics in Italy and Europe between February and June 2020. The cluster analysis showed only small clusters including

IntroductionPatients admitted to the intensive care unit (ICU) following severe acute respiratory syndrome 2 (SARS-CoV-2) infection may have muscle weakness up to 1 year or more following ICU discharge. However, females show greater muscle weakness than males, indicating greater neuromuscular impairment. The objective of this work was to assess sex differences in longitudinal physical functioning following ICU discharge for SARS-CoV-2 infection.MethodsWe performed longitudinal assessment of physical functioning in two groups: 14 participants (7 males, 7 females) in the 3-to-6 month and 28 participants (14 males, 14 females) in the 6-to-12 month group following ICU discharge and assessed differences between the sexes. We examined self-reported fatigue, physical functioning, compound muscle action potential (CMAP) amplitude, maximal strength, and the neural drive to the tibialis anterior muscle.ResultsWe found no sex differences in the assessed parameters in the 3-to-6-month follow-up, indicating significant weakness in both sexes.Sex differences emerged in the 6-to-12-month follow-up. Specifically, females exhibited greater impairments in physical functioning, including lower strength, walking lower distances, and high neural input even 1 year following ICU-discharge.DiscussionFemales infected by SARS-CoV-2 display significant impairments in functional recovery up to 1 year following ICU discharge. The effects of sex should be considered in post-COVID neurorehabilitation.

Introdução: compreender como profissionais da Estratégia Saúde da Família percebem a intoxicação infantil e as práticas de cuidado desenvolvidas em comunidade em situação de vulnerabilidade social. Métodos: pesquisa de abordagem qualitativa baseada no referencial dialógico de Paulo Freire. Foi desenvolvida por entrevistas face a face, com 15 profissionais integrantes de equipes da Estratégia Saúde da Família de um município do Noroeste do Paraná, Brasil. As entrevistas foram áudio gravadas, transcritas e submetidas à Análise de Conteúdo de Bardin. Resultados: as percepções foram articuladas em três categorias temáticas: Intoxicações infantis e o ambiente domiciliar: como os acidentes ocorrem; Prática profissional para atendimento, encaminhamento e prevenção das intoxicações infantis; e Limites para a prática de promoção e prevenção das intoxicações infantis no território. Conclusão: as percepções revelam os profissionais não considerarem a família inserida em um contexto sociocultural como centro da ação profissional, poucos referiam ao cuidado no contexto da promoção da saúde e prevenção.

Abstract Background The causative agent of Chagas disease, Trypanosoma cruzi, and its nonpathogenic relative, Trypanosoma rangeli, are transmitted by haematophagous triatomines and undergo a crucial ontogenetic phase in the insect’s intestine. In the process, the parasites interfere with the host immune system as well as the microbiome present in the digestive tract potentially establishing an environment advantageous for development. However, the coherent interactions between host, pathogen and microbiota have not yet been elucidated in detail. We applied a metagenome shotgun sequencing approach to study the alterations in the microbiota of Rhodnius prolixus, a major vector of Chagas disease, after exposure to T. cruzi and T. rangeli focusing also on the functional capacities present in the intestinal microbiome of the insect. Results The intestinal microbiota of R. prolixus was dominated by the bacterial orders Enterobacterales, Corynebacteriales, Lactobacillales, Clostridiales and Chlamydiales, whereas the latter conceivably originated from the blood used for pathogen exposure. The anterior and posterior midgut samples of the exposed insects showed a reduced overall number of organisms compared to the control group. However, we also found enriched bacterial groups after exposure to T. cruzi as well as T rangeli. While the relative abundance of Enterobacterales and Corynebacteriales decreased considerably, the Lactobacillales, mainly composed of the genus Enterococcus, developed as the most abundant taxonomic group. This applies in particular to vectors challenged with T. rangeli and at early timepoints after exposure to vectors challenged with T. cruzi. Furthermore, we were able to reconstruct four metagenome-assembled genomes from the intestinal samples and elucidate their unique metabolic functionalities within the triatomine microbiome, including the genome of a recently described insect symbiont, Candidatus Symbiopectobacterium, and the secondary metabolites producing bacteria Kocuria spp. Conclusions Our results facilitate a deeper understanding of the processes that take place in the intestinal tract of triatomine vectors during colonisation by trypanosomal parasites and highlight the influential aspects of pathogen-microbiota interactions. In particular, the mostly unexplored metabolic capacities of the insect vector’s microbiome are clearer, underlining its role in the transmission of Chagas disease. Video Abstract

Background: Given the low chance of response to neoadjuvant chemotherapy (NACT) in luminal breast cancer (LBC), the identification of predictive factors of pathological complete response (pCR) represents a challenge. A multicenter retrospective analysis was performed to develop and validate a predictive nomogram for pCR, based on pre-treatment clinicopathological features. Methods: Clinicopathological data from stage I–III LBC patients undergone NACT and surgery were retrospectively collected. Descriptive statistics was adopted. A multivariate model was used to identify independent predictors of pCR. The obtained log-odds ratios (ORs) were adopted to derive weighting factors for the predictive nomogram. The receiver operating characteristic analysis was applied to determine the nomogram accuracy. The model was internally and externally validated. Results: In the training set, data from 539 patients were gathered: pCR rate was 11.3% [95% confidence interval (CI): 8.6–13.9] (luminal A-like: 5.3%, 95% CI: 1.5–9.1, and luminal B-like: 13.1%, 95% CI: 9.8–13.4). The optimal Ki67 cutoff to predict pCR was 44% (area under the curve (AUC): 0.69; p < 0.001). Clinical stage I–II (OR: 3.67, 95% CI: 1.75–7.71, p = 0.001), Ki67 ⩾44% (OR: 3.00, 95% CI: 1.59–5.65, p = 0.001), and progesterone receptor (PR) 1%, and Ki67

BackgroundIn women scheduled for cancer treatment, oocytes cryopreservation is a well-established procedure. Random start protocols have been a substantial improvement in this setting, allowing to prevent delay in the initiation of cancer treatments. However, there is still the need to optimize the regimen of ovarian stimulation, to make treatments more patient-friendly and to reduce costs.MethodsThis retrospective study compares two periods (2019 and 2020), corresponding to two different ovarian stimulation regimens. In 2019, women were treated with corifollitropin, recombinant FSH and GnRH antagonists. Ovulation was triggered with GnRH agonists. In 2020, the policy changed, and women were treated with a progestin-primed ovarian stimulation (PPOS) protocol with human menopausal gonadotropin (hMG) and dual trigger (GnRH agonist and low dose hCG) Continuous data are reported as median [Interquartile Range]. To overcome expected changes in baseline characteristics of the women, the primary outcome was the ratio between the number of mature oocytes retrieved and serum anti-mullerian hormone (AMH) in ng/ml.ResultsOverall, 124 women were selected, 46 in 2019 and 78 in 2020. The ratio between the number of mature oocytes retrieved and serum AMH in the first and second period was 4.0 [2.3-7.1] and 4.0 [2.7-6.8], respectively (p = 0.80). The number of scans was 3 [3-4] and 3 [2-3], respectively (pConclusionsRandom start PPOS with hMG and dual trigger represents an easy and affordable ovarian stimulation protocol for fertility preservation in women with cancer, showing similar efficacy and being more friendly and economical.

BackgroundRhodnius prolixus is a vector of Chagas disease and has become a model organism to study physiology, behavior, and pathogen interaction. The publication of its genome allowed initiating a process of comparative characterization of the gene expression profiles of diverse organs exposed to varying conditions. Brain processes control the expression of behavior and, as such, mediate immediate adjustment to a changing environment, allowing organisms to maximize their chances to survive and reproduce. The expression of fundamental behavioral processes like feeding requires fine control in triatomines because they obtain their blood meals from potential predators. Therefore, the characterization of gene expression profiles of key components modulating behavior in brain processes, like those of neuropeptide precursors and their receptors, seems fundamental. Here we study global gene expression profiles in the brain of starved R. prolixus fifth instar nymphs by means of RNA sequencing (RNA-Seq).ResultsThe expression of neuromodulatory genes such as those of precursors of neuropeptides, neurohormones, and their receptors; as well as the enzymes involved in the biosynthesis and processing of neuropeptides and biogenic amines were fully characterized. Other important gene targets such as neurotransmitter receptors, nuclear receptors, clock genes, sensory receptors, and takeouts genes were identified and their gene expression analyzed.ConclusionWe propose that the set of neuromodulatory-related genes highly expressed in the brain of starved R. prolixus nymphs deserves functional characterization to allow the subsequent development of tools targeting them for bug control. As the brain is a complex structure that presents functionally specialized areas, future studies should focus on characterizing gene expression profiles in target areas, e.g. mushroom bodies, to complement our current knowledge.