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BackgroundPaediatric acute B-cell lymphoblastic leukaemia is the most common cancer of the paediatric age. Although the advancement of scientific and technological knowledge has ensured a huge step forward in the management of this disease, there are 15%–20% cases of recurrence leading to serious complications for the patient and sometimes even death. It is therefore necessary to identify new and increasingly personalised biomarkers capable of predicting the degree of risk of B-ALL in order to allow the correct management of paediatric leukaemia patients.MethodsStarting from our previously published results, we validate the expression level of LINC00958 in a cohort of 33 B-ALL and 9 T-ALL childhood patients, using in-silico public datasets as support. Expression levels of LINC00958 in B-ALL patients stratified by risk (high risk vs. standard/medium risk) and who relapsed 3 years after the first leukaemia diagnosis were also evaluated.ResultsWe identified the lncRNA LINC00958 as a biomarker of B-ALL, capable of discriminating B-ALL from T-ALL and healthy subjects. Furthermore, we associated LINC00958 expression levels with the disease risk classification (high risk and standard risk). Finally, we show that LINC00958 can be used as a predictor of relapses in patients who are usually stratified as standard risk and thus not always targeted for marrow transplantation.ConclusionsOur results open the way to new diagnostic perspectives that can be directly used in clinical practice for a better management of B-ALL paediatric patients.

Biliary endoprostheses are widely used in the treatment of biliary lithiasis, malignant and benign strictures, and occasionally in long-lasting biliary fistulas. They can be placed endoscopically during endoscopic retrograde cholangiopancreatography and radiologically (percutaneous) when the endoscopic route is not feasible. Complications associated with the endoscopic placement of biliary endoprostheses are well described in the literature, with migration being the most common. Intestinal obstruction is a rare complication associated with the migration of these devices. There are no reports in the literature of this complication occurring after percutaneous placement. We present a case of a patient who arrived at the emergency department with ileal obstruction secondary to the migration and concurrent embedding of a covered stent placed radiologically to treat a biliary leak after surgery. The patient underwent diagnostic laparoscopic and ileal resection, revealing a lithiasic concretion at the tip of the stent, causing the small bowel obstruction.

In the present work, synthetic slags (FeO-SiO2-CaO-P2O5-Al2O3-TiO2-V2O5 system) mimicking the composition of the slag inclusions of Ipanema were solidified at different cooling rates. FactSage software was used to calculate the slag’s phase equilibria from 500ºC to 1600°C to guide the microstructural characterisation. The samples solidified with slower cooling rates featured wüstite dendrites and a eutectic-like matrix, with intradendritic (Al,V,Ti)-containing iron spinel precipitates in the wüstite. The rapidly solidified slag showed refined wüstite dendrites surrounded by a Fe-O-Si-Ca-containing amorphous single-phase matrix without intradendritic (Al,V,Ti)-containing iron spinel precipitation. The comparison of the calculated phase diagram with the as-cast microstructures showed a few discrepancies. For instance, the FactSage’s database must be updated to consider the simultaneous solubility of Al, V and Ti in the thermodynamic description of the spinel phases, such as FToxid-SP-V, FToxid-SPINA, FToxid-TiSp and (FeO)2(TiO2)(s). Finally, the intradendritic precipitation of (Al,V,Ti)-containing iron spinel phases in the wüstite of the slag inclusions indicated that an Ipanema’s iron artefact was exposed to high service temperatures between 750 and 1050ºC.

Background: Acute small bowel obstruction (aSBO) is the most common cause (76%) of acute intestinal obstruction. Laparoscopy use is still controversial in aSBO and indications not yet clearly defined. The aim of this study was to demonstrate the effectiveness and safety of a laparoscopic approach in aSBO by using specific pre-operative criteria for appropriate patient selection. Methods: We retrospectively analyzed medical records of patients accepted at the Emergency Department for aSBO between January 2016 and March 2021 and performed a comparative analysis between types of treatment, considering demographics, clinical and radiological presentation, non-operative vs. operative management, intraoperative outcome, and postoperative course. We used a logistic regression to identify the variables related to surgical approach and built a predictive score upon the multivariable predictive model: the “SABO score”. Results: 198 patients were included in the study, of which 145 underwent surgery and 43 were successfully treated laparoscopically. Age and comorbidities were associated with open surgery (OR 3.2, 95% CI: 1.4–7.2, p = 0.006 and OR 2.7, 95% CI: 1.1–6.5, p = 0.023). A SABO score ≥ 0 identified an open approach with a sensitivity of 75.4% and a specificity of 69.8%. Conclusions: Laparoscopy is growing in importance even in emergency settings. Our analysis suggests that a laparoscopic approach can be safe and feasible in aSBO management. Correct patient selection appears to be the key for a successful minimally invasive approach. SABO score therefore could be helpful in choosing the correct surgical strategy for patients with aSBO.

Abstract Background Long non-coding RNAs are RNAs longer than 200 bps that do not encode any proteins and are able to alter gene expression by acting on different steps of regulation, including DNA methylation and chromatin structure. They represent a class of biomarkers of crescent interest in the hematologic and oncologic fields. Recent studies showed that the expression levels of specific lncRNAs correlate with the prognosis of paediatric patients with Acute Lymphoblastic Leukaemia. Methods We used NGS approaches to analyse the transcriptome of 9 childhood B-ALL patients and 6 childhood T-ALL patients, in comparison with B and T healthy lymphocytes from cord blood. We validate our findings both ex vivo, in a different cohort of 10 B-ALL and 10 T-ALL patients, and in silico using public datasets. Results We characterised the lncRNA landscape for B-ALL, T-ALL, healthy B, and T cell progenitors. From the characterised signature, we selected candidate lncRNAs able to discriminate not only B-ALL and T-ALL from healthy subjects but also between the two types of leukaemia, and subsequently validated their potential as a diagnostic tool in an additional cohort of paediatric patients. We confirmed our finding with open access transcriptomic data, comparing ALL lncRNAs with AML lncRNA landscape as well. Finally, expression correlation analyses of T-ALL selected lncRNA biomarkers suggested a possible role in lymphocyte activation and the β-catenin signalling pathway for AC247036.1 and involvement in hedgehog signalling for HHIP-AS1. Conclusions Our work identified a lncRNA signature discriminating paediatric B-ALL and T-ALL from healthy subjects, between them and from AML. This study provides the keystone to future clinical studies determining the theragnostic value of the characterised long non coding transcriptome panorama in a clinical setting for childhood patient management.

(1) Background: Preeclampsia (PE) usually presents with hypertension and proteinuria, related to poor placentation. Reduced maternal–fetal immunological tolerance is a possible trigger of inadequate placentation. Aberrant antigen expression of HLA-DR has been observed in the syncytiotrophoblast of PE patients. In this study, we analyzed plasma levels of Human Leukocyte Antigen (HLA)-DR+ syncytiotrophoblast-derived extracellular vesicles (STEVs) during the three trimesters of pregnancy in relation to PE onset. (2) Methods: Pregnant women underwent venous blood sampling during the three trimesters. STEVs were collected from plasma via ultracentrifugation (120,000 g) and characterized by Western blot, nanotracking analysis and flow cytometry for the expression of Placental Alkaline Phosphatase (PLAP), a placental-derived marker, and HLA-DR. (3) Results: Out of 107 women recruited, 10 developed PE. STEVs were detected in all three trimesters of pregnancy with a zenith in the second trimester. A significant difference was found between the non-PE and PE groups in terms of plasma levels of HLA-DR+ STEVs during all three trimesters of pregnancy. (4) Conclusions: More research is needed to investigate HLA-DR+ as a potential early marker of PE.

The prevalence of mitral (MR) and tricuspid regurgitation (TR), especially in heart failure (HF) populations, is high. However, the distinct role of atrioventricular valve diseases in HF, whether they are merely indicators of disease status or rather independent contributors in a vicious disease cycle, is still not fully understood. For decades, tricuspid regurgitation (TR) was considered an innocent bystander subsequent to other heart or lung pathologies, thus, not needing dedicated treatment. Recent increasing awareness towards the role of atrioventricular valve diseases has revealed that MR and TR are, in fact, independent predictors of outcome in HF, thus, warranting attention in the HF treatment algorithm. This awareness arose, especially, with the development of minimally invasive transcatheter solutions providing new treatment options, which can also be used for patients considered as having increased surgical risk. However, outcomes of such transcatheter treatments have, in part, been sub-optimal and likely influenced by the status of the concomitant HF disease. Thus, this review aims to summarize data on the current understanding regarding the role of MR and TR in HF, how HF impacts outcomes of transcatheter MR and TR interventions, and how the understanding of this relationship might help to identify patients that benefit most from these therapies, which have proven to be lifesaving in properly selected candidates.

Over the past few years, transcatheter aortic valve implantation (TAVI) imposed itself as the first-choice therapy for symptomatic aortic stenosis (AS) in elderly patients at surgical risk. There have been continuous technological advancements in the latest iterations of TAVI devices and implantation techniques, which have bolstered their adoption. Moreover, the favorable outcomes coming out from clinical trials represent an indisputable point of strength for TAVI. As indications for transcatheter therapies now include a low surgical risk and younger individuals, new challenges are emerging. In this context, the matter of prosthesis durability is noteworthy. Initial evidence is beginning to emerge from the studies in the field, but they are still limited and compromised by multiple biases. Additionally, the physiopathological mechanisms behind the valve's deterioration are nowadays somewhat clearer and classified. So, who outlasts who—the valve or the patient? This review aims to explore the available evidence surrounding this intriguing question, examining the various factors affecting prosthesis durability and discussing its potential implications for clinical management and current interventional practice. [ABSTRACT FROM AUTHOR]

Lung ultrasound has been recognized as a valid imaging method for diagnosing and monitoring COVID-19 pneumonia in pregnant women. The present review aimed to summarize the main findings reported in the literature and international guidelines on the role of lung ultrasound in the care of pregnant women affected by COVID-19. A search strategy was developed and applied to PubMed, Scopus, Web of Science and EMBASE to identify previous papers reporting the utility of ultrasound in diagnosing and monitoring COVID-19 pneumonia. The search retrieved 369 articles and 23 of these were selected for analysis. The articles mainly focused on the definition of the procedure, development of training programs for obstetricians managing pregnant women with suspicion of COVID-19 and definition of scoring systems. The clinical applications of lung ultrasound in this setting have also been described. This review could encourage obstetricians to learn lung ultrasound to use during critical events like a pandemic.

Abstract Like other KCTD proteins, KCTD15 is involved in important albeit distinct biological processes as cancer, neural crest formation, and obesity. Here, we characterized the role of KCTD15 in different physiological/pathological states to gain insights into its diversified function(s). The silencing of KCTD15 in MLL-rearranged leukemia models induced attenuation of the NF-κB pathway associated with a downregulation of pIKK-β and pIKB-α. Conversely, the activation of peripheral blood T cells upon PMA/ionomycin stimulation remarkably upregulated KCTD15 and, simultaneously, pIKK-β and pIKB-α. Moreover, a significant upregulation of KCTD15 was also observed in CD34 hematopoietic stem/progenitor cells where the NF-κB pathway is physiologically activated. The association between KCTD15 upregulation and increased NF-κB signaling was confirmed by luciferase assay as well as KCTD15 and IKK-β proximity ligation and immunoprecipitation experiments. The observed upregulation of IKK-β by KCTD15 provides a novel and intriguing interpretative key for understanding the protein function in a wide class of physiological/pathological conditions ranging from neuronal development to cancer and obesity/diabetes.

Abstract The article reviews the metallurgical processes used in the first industrial ironworks operated in Brazil, the Patriótica Iron Factory, from 1812 to 1831. It discusses its impact on the ironmaking plants that spread in Minas Gerais's state during the XIX century. The remnants of this Factory in Ouro Preto were the first industrial site listed by the Brazilian Historic Heritage Authority (SPHAN) in 1938. Vale SA, owner of the site, and the National Historic and Artistic Heritage Institute (IPHAN) authorised collecting samples from two ferrous artefacts found in the old Factory, a hammer and an eyebolt nailed to the remnants of one of the reduction furnaces. The eyebolt’s microstructure suggests that this part was produced in the Patriótica Iron Factory, while the hammer’s microstructure indicates that this component was not produced in the Patriótica Iron Factory.

Isolated tricuspid regurgitation (TR) has gained increasing recognition in recent years both in the surgical and in the cardiological community. Left untreated, isolated TR significantly worsens survival. Despite being a strong predictor of negative prognosis, interventions to correct TR are rarely performed due to increased surgical risk and late patient presentation. Recently, the ultimate focus has been on patient selection, surgical or transcatheter indication, and correct timing. Furthermore, of paramount importance is the identification of predictors of outcome following treatment, in order to discriminate between favorable and unfavorable responders and guide the decision-making process of the most adequate treatment for every patient.

Immunoglobulin (IgG) Fc glycosylation has been shown to be important for the biological activity of antibodies. Fc sialylation is important for the anti-inflammatory activity of IgGs. However, evaluating the structure–activity relationship (SAR) of antibody Fc glycosylation has been hindered using simplified in vitro models in which antibodies are often displayed in monomeric forms. Presenting antibodies in monomeric forms may not accurately replicate the natural environment of the antibodies when binding their antigen in vivo. To address these limitations, we used different Fc-containing molecules, displaying their Fc domains in monovalent and multivalent fashion. Given the inhibitory role of Fc gamma receptor IIb (FcγRIIb) in autoimmune and inflammatory diseases, we focused on evaluating the impact of Fc sialylation on the activation of FcγRIIb. We report for the first time that in human cellular systems, sialic acid mediates the induction of FcγRIIb phosphorylation by IgG-Fc when the IgG-Fc is displayed in a multivalent fashion. This effect was observed with different types of therapeutic agents such as sialylated anti-TNFα antibodies, sialylated IVIg and sialylated recombinant multivalent Fc products. These studies represent the first report of the specific effects of Fc sialylation on FcγRIIb signaling on human immune cells and may help in the characterization of the anti-inflammatory activity of Fc-containing therapeutic candidates.

Abstract Background Long non-coding RNAs (lncRNAs) represent a diverse class of RNAs involved in the regulation of various physiological and pathological cellular processes, including transcription, intracellular trafficking, and chromosome remodeling. LncRNAs deregulation was linked to the development and progression of various cancer types, such as acute leukemias. In this context, lncRNAs were also evaluated as a novel class of biomarkers for cancer diagnosis and prognosis. Here, we analyzed TEX41 in childhood B cell acute lymphoid leukemia (B-ALL). Methods Total RNA was extracted from pediatric B-ALL patients (at diagnosis and after induction of therapy) and from healthy subjects. Total RNA was also extracted from different leukemia cell line models. The expression level of TEX41 was evaluated by q-RT-PCR. Also, the dataset deposited by St. Jude Children’s Research Hospital was consulted. Furthermore, the silencing of TEX41 in RS4;11 cell line was obtained by 2′-Deoxy, 2′Fluroarabino Nucleic Acids (2′F-ANAs) Oligonucleotides, and the effect on cell proliferation was evaluated. Cell cycle progression and its regulators were analyzed by flow cytometry and immunoblotting. Results We exploited the St Jude Cloud database and found that TEX41 is a lncRNA primarily expressed in the case of B-ALL (n = 79) while its expression levels are low/absent for T-cell ALL (n = 25) and acute myeloid leukemia (n = 38). The association of TEX41 with B-ALL was confirmed by real-time PCR assays. TEX41 disclosed increased expression levels in bone marrow from patients with B-ALL at diagnosis, while its expression levels became low or absent when retested in Bone Marrow cells of the same patient after 1 month of induction therapy. Also, silencing experiments performed on RS4;11 cells showed that TEX41 downregulation impaired in vitro leukemic cell growth determining their arrest in the G2-M phase and the deregulation of cell cycle proteins. Conclusions Our findings highlight that TEX41 is an upregulated lncRNA in the case of B-ALL and this feature makes it a novel potential biomarker for the diagnosis of this leukemia subtype in pediatric patients. Finally, TEX41 expression seems to be critical for leukemic proliferation, indeed, silencing experiments targeting TEX41 mRNA in the RS4;11 cell line hampered in vitro cell growth and cell cycle progression, by inducing G2-M arrest as confirmed propidium iodide staining and by the upregulation of p53 and p21 proteins.

Witchcraft has been described as knowledge that resists knowledge. Drawing on our field research on witchcraft, alienation, and violence in Mali and southern Cameroon as well as with migrants coming from sub-Saharan Africa, we consider two main issues. The first concerns the epistemic challenge of 'witchcraft' and its satellite notions (mystical weapons, animal metamorphosis, fetish and so forth). We analyse this 'challenge' beyond the problems of translation, both as a particular expression of African perspectivism and an unending struggle concerning epistemic sovereignty. The second issue directly originates from our field research. Prudently, we will try to give a new lease of life to an ethnographic material, studied 20 years ago. We would turn back to some drawings made by students at the primary school of Mbom (Sangmelina, southern Cameroon), and explore the power of what we provisionally define as 'visual utterances'. [ABSTRACT FROM AUTHOR]

Abstract The occurrence of protozoan parasite, bacterial communities, organic pollutants and heavy metals was investigated in free-ranging species of fin (Balaenoptera physalus, n. 2) and sperm (Physeter macrocephalus, n. 2) whales from the Pelagos Sanctuary, Corsican-Ligurian Provencal Basin (Northern-Western Mediterranean Sea). Out of four faecal samples investigated, two from fin whales and one from sperm whale were found positive to Blastocystis sp. A higher number of sequences related to Synergistetes and Spirochaetae were found in sperm whales if compared with fin whales. Moreover, As, Co and Hg were found exclusively in sperm whale faecal samples, while Pb was found only in fin whale faecal samples. The concentration of both PAH and PCB was always below the limit of detection. This is the first report in which the presence of these opportunistic pathogens, bacteria and chemical pollutants have been investigated in faecal samples of free-ranging whale species and the first record of Blastocystis in fin and sperm whales. Thus, this study may provide baseline data on new anthropozoonotic parasite, bacterial records and heavy metals in free-ranging fin and sperm whales, probably as a result of an increasing anthropogenic activity. This survey calls for more integrated research to perform regular monitoring programs supported by national and/or international authorities responsible for preservation of these still vulnerable and threatened whale species in the Mediterranean Sea.

Nucleation in systems with a metastable liquid–gas critical point is the prototypical example of a two-step nucleation process in which the appearance of the critical nucleus is preceded by the formation of a liquid-like density fluctuation. So far, the majority of studies on colloidal and protein crystallization have focused on one-component systems, and we are lacking a clear description of two-step nucleation processes in multicomponent systems, where critical fluctuations involve coupled density and concentration inhomogeneities. Here, we examine the nucleation process of a binary mixture of patchy particles designed to nucleate into a diamond lattice. By combining Gibbs-ensemble simulations and direct nucleation simulations over a wide range of thermodynamic conditions, we are able to pin down the role of the liquid–gas metastable phase diagram on the nucleation process. In particular, we show that the strongest enhancement of crystallization occurs at an azeotropic point with the same stoichiometric composition of the crystal. [ABSTRACT FROM AUTHOR]

The impacts of climate change are accelerating worldwide, but emergency agencies and political bodies are not always equipped to anticipate where, when, or how severe the next unnatural disaster will be. Amid megafire seasons, for example, scientists are revising models of fire behavior that were calibrated to natures that increasingly diverge from known baselines and trends. Emergency responders' trust in patterns has become an occupational hazard. At these edges of knowledge, struggles to maintain responsive capacity in disrupted ecologies are at play; a larger reckoning with runaway climate change as a relational problem space is in order. Rather than making me resort to despair about the world's "end," such labors redirect my attention toward horizons of expectation in which knowledges are still actionable, not obsolete, and where capacities for future interventions are viable and not denied. These activities, enmeshed in a rubric of horizon work, shift expert authority and promote critical realignments across political, activist, and Indigenous spheres. [ABSTRACT FROM AUTHOR]

Background: Paediatric acute B-cell lymphoblastic leukaemia is the most common cancer of the paediatric age. Although the advancement of scientific and technological knowledge has ensured a huge step forward in the management of this disease, there are 15%–20% cases of recurrence leading to serious complications for the patient and sometimes even death. It is therefore necessary to identify new and increasingly personalised biomarkers capable of predicting the degree of risk of B-ALL in order to allow the correct management of paediatric leukaemia patients. Methods: Starting from our previously published results, we validate the expression level of LINC00958 in a cohort of 33 B-ALL and 9 T-ALL childhood patients, using in-silico public datasets as support. Expression levels of LINC00958 in B-ALL patients stratified by risk (high risk vs. standard/medium risk) and who relapsed 3 years after the first leukaemia diagnosis were also evaluated. Results: We identified the lncRNA LINC00958 as a biomarker of B-ALL, capable of discriminating B-ALL from T-ALL and healthy subjects. Furthermore, we associated LINC00958 expression levels with the disease risk classification (high risk and standard risk). Finally, we show that LINC00958 can be used as a predictor of relapses in patients who are usually stratified as standard risk and thus not always targeted for marrow transplantation. Conclusions: Our results open the way to new diagnostic perspectives that can be directly used in clinical practice for a better management of B-ALL paediatric patients. [ABSTRACT FROM AUTHOR]

Characterized by a series of operations aimed at restoring the original performance of an industrial manufact, remanufacturing requires products to be designed and optimized to meet the requirements of this process. This article explores the integration of specific remanufacturing requirements in the context of the redesign and structural optimization of machine components. Based on the analysis of a study case remanufacturing process, conducted by a leading company in the field of agricultural machinery, the main objective of this work is to propose new remanufacturing evaluation indices and criteria for selecting components to be redesigned, based on these indices. The proposed key performance indicators (KPIs), expressed in terms of structural characteristics of assembly components such as incidence and failure rate, have been defined with the primary purpose of quantifying the weight in terms of quantity and mass of remanufactured components and assemblies against the overall industry production. This value can serve as the basis for choices and structural optimization operations, leading to increased efficiency in the remanufacturing process and, consequently, the correlated environmental and economic benefits. The indices described and proposed in this article, along with the approach taken, are intended to provide tools and guidelines to the industries to be used in the redesign phase of their products intended for remanufacturing. [ABSTRACT FROM AUTHOR]

Background Controversy exists over whether sex has significant interaction with revascularization strategy for unprotected left main coronary artery disease. Higher mortality has been reported among women treated with percutaneous coronary intervention compared with coronary artery bypass grafting. Methods and Results The DELTA (Drug‐Eluting Stents for Left Main Coronary Artery Disease) and DELTA‐2 registries are international, multicentric registries evaluating the outcomes of subjects undergoing coronary revascularization for unprotected left main coronary artery disease. The primary outcome was a composite of death, myocardial infarction, or cerebrovascular accidents. The population consisted of 6253 patients, including 1689 (27%) women. Women were older and more likely to have diabetes and chronic kidney disease than men (P

The coronavirus disease-2019 (COVID-19) pandemic has caused an enormous strain on healthcare systems and society on a global scale. We report a new phenomenon of medical care avoidance among patients with acute coronary syndrome, which is due to concerns about contracting severe acute respiratory syndrome-coronavirus-2 (SARS-CoV-2) infection during hospital stay, ultimately leading to dire clinical outcomes. (Level of Difficulty: Beginner.)