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IntroductionRecent evidence suggests that the bone marrow (BM) plays a key role in the diffusion of P. falciparum malaria by providing a “niche” for the maturation of the parasite gametocytes, responsible for human-to-mosquito transmission. Suitable humanized in vivo models to study the mechanisms of the interplay between the parasite and the human BM components are still missing.MethodsWe report a novel experimental system based on the infusion of immature P. falciparum gametocytes into immunocompromised mice carrying chimeric ectopic ossicles whose stromal and bone compartments derive from human osteoprogenitor cells.ResultsWe demonstrate that immature gametocytes home within minutes to the ossicles and reach the extravascular regions, where they are retained in contact with different human BM stromal cell types.DiscussionOur model represents a powerful tool to study BM function and the interplay essential for parasite transmission in P. falciparum malaria and can be extended to study other infections in which the human BM plays a role.

Abstract In early childhood, air pollution leads to an increased risk of disease, premature death, and development of disruptions. Fine particulate matter (PM2.5) is considered the classical pollutant of major concern. However, in Brazil, fine particulate monitoring is still limited and restricted to a few cities. Particularly, in the city of Rio de Janeiro, only one automatic station obtains PM2.5 concentrations and publishes the air quality indexes daily. This study is part of the project “Clean air for a good start” managed by the Horizon Citizen Foundation, with the goal of obtaining evidence to set a plan to reduce children exposition to air pollution. Data is shared on a global web platform. Results showed that PM2.5 levels are high when compared with WHO guidelines and coordinated actions would be needed to decrease emissions of primary pollutants and secondary aerosol’s precursors.

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Drug repurposing is a valuable strategy for rare diseases. Sickle cell disease (SCD) is a rare hereditary hemolytic anemia accompanied by acute and chronic painful episodes, most often in the context of vaso-occlusive crisis (VOC). Although progress in the knowledge of pathophysiology of SCD have allowed the development of new therapeutic options, a large fraction of patients still exhibits unmet therapeutic needs, with persistence of VOCs and chronic disease progression. Here, we show that imatinib, an oral tyrosine kinase inhibitor developed for the treatment of chronic myelogenous leukemia, acts as multimodal therapy targeting signal transduction pathways involved in the pathogenesis of both anemia and inflammatory vasculopathy of humanized murine model for SCD. In addition, imatinib inhibits the platelet-derived growth factor-B–dependent pathway, interfering with the profibrotic response to hypoxia/reperfusion injury, used to mimic acute VOCs. Our data indicate that imatinib might be considered as possible new therapeutic tool for chronic treatment of SCD.

The first low-energy Coulomb-excitation measurement of the radioactive, semi-magic, two proton-hole nucleus 206Hg, was performed at CERN's recently-commissioned HIE-ISOLDE facility. Two γ rays depopulating low-lying states in 206Hg were observed. From the data, a reduced transition strength B(E2;21+→01+)=4.4(6) W.u. was determined, the first such value for an N=126 nucleus south of 208Pb, which is found to be slightly lower than that predicted by shell-model calculations. In addition, a collective octupole state was identified at an excitation energy of 2705 keV, for which a reduced B(E3) transition probability of 30−13+10 W.u. was extracted. These results are crucial for understanding both quadrupole and octupole collectivity in the vicinity of the heaviest doubly-magic nucleus 208Pb, and for benchmarking a number of theoretical approaches in this key region. This is of particular importance given the paucity of data on transition strengths in this region, which could be used, in principle, to test calculations relevant to the astrophysical r-process.

At the beginning of the 2020 pandemic, I grew concerned and also curious about how theatre educators would transition theatre and drama instruction to an online platform. I began a research study interviewing theatre artists while they shifted their formerly in-person summer camps to virtual spaces. One of those instructors, Flannery, was initially hesitant to accept online learning, but through her experiences teaching camps and our conversations, she came to embrace Zoom, an online platform, for its strengths. Through this exploration, I, too, grew more confident that online platforms during this time could be an effective teaching, learning, and performance tool for theatre.

Abstract Endangered animals in captivity may display reduced brain sizes due to captive conditions and limited genetic diversity. Captive diets, for example, may differ in nutrition and texture, altering cranial musculature and alleviating constraints on cranial shape development. Changes in brain size are associated with biological fitness, which may limit reintroduction success. Little is known about how changes in brain size progress in highly managed carnivoran populations and whether such traits are retained among reintroduced populations. Here, we measured the endocranial volume of preserved Mexican wolf skulls across captive generations and between captive, wild, and reintroduced populations and assessed endocranial volume dependence on inbreeding and cranial musculature. Endocranial volume increased across captive generations. However, we did not detect a difference among captive, wild, and reintroduced groups, perhaps due to the variability across captive generations. We did not find a relationship between endocranial volume and either inbreeding or cranial musculature, although the captive population displayed an increase in the cross-sectional area of the masseter muscle. We hypothesize that the increase in endocranial volume observed across captive generations may be related to the high-quality nutrition provided in captivity.

Davide Benedetti,1 Umberto Olcese,2 Simone Bruno,1 Marta Barsotti,3 Michelangelo Maestri Tassoni,3,4 Enrica Bonanni,3,4 Gabriele Siciliano,3,4 Ugo Faraguna1,5 1Department of Translational Research and of New Surgical and Medical Technologies, University of Pisa, Pisa, Italy; 2Cognitive and Systems Neuroscience Group, Swammerdam Institute for Life Sciences, University of Amsterdam, Amsterdam, the Netherlands; 3Neurological Clinics, University Hospital of Pisa, Pisa, Italy; 4Department of Clinical and Experimental Medicine, University of Pisa, Pisa, Italy; 5Department of Developmental Neuroscience, IRCCS Fondazione Stella Maris, Pisa, ItalyCorrespondence: Ugo Faraguna, Department of Translational Research and of New Surgical and Medical Technologies, University of Pisa, Via San Zeno, 31, Pisa, 56123, Italy, Tel +39 050 2213470, Email ugo.faraguna@unipi.itPurpose: A large portion of the adult population is thought to suffer from obstructive sleep apnoea syndrome (OSAS), a sleep-related breathing disorder associated with increased morbidity and mortality. International guidelines include the polysomnography and the cardiorespiratory monitoring (CRM) as diagnostic tools for OSAS, but they are unfit for a large-scale screening, given their invasiveness, high cost and lengthy process of scoring. Current screening methods are based on self-reported questionnaires that suffer from lack of objectivity. On the contrary, commercial smartbands are wearable devices capable of collecting accelerometric and photoplethysmographic data in a user-friendly and objective way. We questioned whether machine-learning (ML) classifiers trained on data collected through these wearable devices would help predict OSAS severity.Patients and Methods: Each of the patients (n = 78, mean age ± SD: 57.2 ± 12.9 years; 30 females) underwent CRM and concurrently wore a commercial wrist smartband. CRM’s traces were scored, and OSAS severity was reported as apnoea hypopnoea index (AHI). We trained three pairs of classifiers to make the following prediction: AHI < 5 vs AHI ≥ 5, AHI < 15 vs AHI ≥ 15, and AHI < 30 vs AHI ≥ 30.Results: According to the Matthews correlation coefficient (MCC), the proposed algorithms reached an overall good correlation with the ground truth (CRM) for AHI < 5 vs AHI ≥ 5 (MCC: 0.4) and AHI < 30 vs AHI ≥ 30 (MCC: 0.3) classifications. AHI < 5 vs AHI ≥ 5 and AHI < 30 vs AHI ≥ 30 classifiers’ sensitivity, specificity, positive predictive values (PPV), negative predictive values (NPV) and diagnostic odds ratio (DOR) are comparable with the STOP-Bang questionnaire, an established OSAS screening tool.Conclusion: Machine learning algorithms showed an overall good performance. Unlike questionnaires, these are based on objectively collected data. Furthermore, these commercial devices are widely distributed in the general population. The aforementioned advantages of machine-learning algorithms applied to smartbands’ data over questionnaires lead to the conclusion that they could serve a population-scale screening for OSAS.Keywords: obstructive sleep apnoea syndrome, screening, wearable devices, wrist-worn smartbands, artificial intelligence

Platelet reactivity (PR) has been indicated as a pathophysiological key element for ST-Elevation Myocardial Infarction (STEMI) development. Patients with not-high before-treatment platelet reactivity (NHPR) have been poorly studied so far. The aim of this study is to investigate the prevalence, clinical characteristics, response to therapy and outcomes of baseline prior to treatment NHPR among patients with STEMI undergoing primary PCI. We analyzed the data from 358 STEMI patients with assessment of PR by VerifyNow before P2Y12 inhibitor loading dose (LD). Blood samples were obtained at baseline, and after 1 hour, 2 hours, 4–6 hours and 8–12 hours after LD. High platelet reactivity (HPR) was defined as Platelet Reactivity Unit values ≥208, while patients with values

Ataxia is increasingly being recognized as a cardinal manifestation in primary mitochondrial diseases (PMDs) in both paediatric and adult patients. It can be caused by disruption of cerebellar nuclei or fibres, its connection with the brainstem, or spinal and peripheral lesions leading to proprioceptive loss. Despite mitochondrial ataxias having no specific defining features, they should be included in hereditary ataxias differential diagnosis, given the high prevalence of PMDs. This review focuses on the clinical and neuropathological features and genetic background of PMDs in which ataxia is a prominent manifestation.

Abstract As metagenomic approaches for detecting infectious agents have improved, each tissue that was once thought to be sterile has been found to harbor a variety of microorganisms. Controversy still exists over the status of amniotic fluid, which is part of an immunologically privileged zone that is required to prevent maternal immune system rejection of the fetus. Due to this privilege, the exclusion of microbes has been proposed to be mandatory, leading to the sterile womb hypothesis. Since nucleic acid yields from amniotic fluid are very low, contaminating nucleic acid found in water, reagents and the laboratory environment frequently confound attempts to address this hypothesis. Here we present metagenomic criteria for microorganism detection and a metagenomic method able to be performed with small volumes of starting material, while controlling for exogenous contamination, to circumvent these and other pitfalls. We use this method to show that human mid-gestational amniotic fluid has no detectable virome or microbiome, supporting the sterile womb hypothesis.

Among deregulated microRNAs (miRs) in human malignancies, miR-221 has been widely investigated for its oncogenic role and as a promising biomarker. Moreover, recent evidence suggests miR-221 as a fine-tuner of chronic liver injury and inflammation-related events. Available information also supports the potential of miR-221 silencing as promising therapeutic intervention. In this systematic review, we selected papers from the principal databases (PubMed, MedLine, Medscape, ASCO, ESMO) between January 2012 and December 2020, using the keywords “miR-221” and the specific keywords related to the most important hematologic and solid malignancies, and some non-malignant diseases, to define and characterize deregulated miR-221 as a valuable therapeutic target in the modern vision of molecular medicine. We found a major role of miR-221 in this view.

The IBIS ECO prototype platform is introduced here as a Decision Support System (DSS) designed to intelligently monitor and efficient management of the energetic performance and comfort of existing buildings. This innovative DSS is user-friendly and prioritizes sustainability by employing wireless IoT equipment that automatically adjusts to each building's unique characteristics. Through integration with IoT networks, big data infrastructure, algorithms, and advanced artificial intelligence models, IBIS ECO conducts predictive analysis, identifying anomalies and discomfort situations at an early stage. During the research phase, the prototype drew insights from two distinct case studies in Basilicata, in southern Italy: a primary school classroom and a university classroom with varying occupancy rates, usage patterns, plant system, and environmental conditions. In its development, IBIS ECO focused on creating customizable dashboards and smart applications to effectively monitor and manage environmental and energy parameters, including microclimatic conditions, resource usage, and infrastructure. Moreover, IBIS ECO serves as a comprehensive tool for energy managers, maintainers, and building occupants, promoting continuous monitoring and enhancing well-being and energy efficiency both indoors and outdoors. Its data-driven approach empowers users' awareness to make informed decisions, leading to energy savings, environmental sustainability, and improved living conditions. [ABSTRACT FROM AUTHOR]

Primary mitochondrial diseases (PMDs) are complex group of metabolic disorders caused by genetically determined impairment of the mitochondrial oxidative phosphorylation (OXPHOS). The unique features of mitochondrial genetics and the pivotal role of mitochondria in cell biology explain the phenotypical heterogeneity of primary mitochondrial diseases and the resulting diagnostic challenges that follow. Some peculiar features (“red flags”) may indicate a primary mitochondrial disease, helping the physician to orient in this diagnostic maze. In this narrative review, we aimed to outline the features of the most common mitochondrial red flags offering a general overview on the topic that could help physicians to untangle mitochondrial medicine complexity.

Crocin, a glycoside carotenoid that exhibits several health benefits, is mainly obtained from saffron (Crocus sativus L.), whose quality and content of phytochemicals can be strongly affected by environmental conditions. Therefore, in this work, the crocin content and in vitro antioxidant activity of saffron extracts obtained from three different varieties (Greek, Sicilian, and Iranian saffron) were assessed. Crocin content in saffron extracts was quantified via ultra-performance liquid chromatography coupled with mass spectrometry. The antioxidant activity of saffron extracts was evaluated using the oxygen radical absorbance capacity (ORAC) assay and nitric oxide (NO) radical scavenging test. The Maillard reaction was used to assess anti-glycation activity. Although the Sicilian and Iranian saffron extracts contained higher amounts of crocin (128 ± 6 ng/mL and 126 ± 4 ng/mL, respectively) compared to the Greek extracts (111 ± 2 ng/mL), ORAC values (50.9 ± 0.5) and % NO inhibition (35.2 ± 0.2) were higher for the Greek variety, which displayed a total phenolic content about two-fold greater than that of the other two extracts. Sicilian and Greek saffron had similar anti-glycation activities, while Iranian saffron was less effective. These results suggest that the antioxidant activity of saffron extracts could be ascribed to their naturally occurring complex mixture of phytochemicals, deserving further investigation as supplements to prevent pathological conditions induced by radical species.

The screening and early diagnosis of diseases are crucial for a patient’s treatment to be successful and to improve their survival rate, especially for cancer. The development of non-invasive analytical methods able to detect the biomarkers of pathologies is a critical point to define a successful treatment and a good outcome. This study extensively reviews the electrochemical methods used for the development of biosensors in a liquid biopsy, owing to their ability to provide a rapid response, precise detection, and low detection limits. We also discuss new developments in electrochemical biosensors, which can improve the specificity and sensitivity of standard analytical procedures. Electrochemical biosensors demonstrate remarkable sensitivity in detecting minute quantities of analytes, encompassing proteins, nucleic acids, and circulating tumor cells, even within challenging matrices such as urine, serum, blood, and various other body fluids. Among the various detection techniques used for the detection of cancer biomarkers, even in the picogram range, voltammetric sensors are deeply discussed in this review because of their advantages and technical characteristics. This widespread utilization stems from their ability to facilitate the quantitative detection of ions and molecules with exceptional precision. A comparison of each electrochemical technique is discussed to assist with the selection of appropriate analytical methods.

Acute pancreatitis (AP) is an acute inflammation of the pancreas caused by the activation of digestive enzymes in the pancreatic tissue. The main causes of AP are cholelithiasis and alcohol abuse; less commonly, it can be caused by drugs, with a prevalence of up to 5%. Causal associations between drugs and pancreatitis are largely based on case reports or case series with limited evidence. We reviewed the available data on drug-induced AP, focusing on antimicrobial drugs and antivirals, and discussed the current evidence in relation to the classification systems available in the literature. We found 51 suspected associations between antimicrobial and antiviral drugs and AP. The drugs with the most evidence of correlation are didanosine, protease inhibitors, and metronidazole. In addition, other drugs have been described in case reports demonstrating positive rechallenge. However, there are major differences between the various classifications available, where the same drug being assigned to different probability classes. It is likely that the presence in multiple case reports of an association between acute pancreatitis and a drug should serve as a basis for conducting prospective randomized controlled trials to improve the quality of the evidence.

Background and Objectives: Treatment of visceral artery pseudoaneurysms (VAPs) is always indicated regardless of their diameters, as their risk of rupture is significantly higher than that of visceral artery aneurysms. The invasiveness of surgery and its associated complications have led to a shift in favor of radiological interventions as the initial treatment of choice. However, there are still some unanswered questions on endovascular treatment of VAPs regarding the optimal endovascular technique and the efficacy and safety outcomes. The purpose of this multicenter study was to retrospectively evaluate the effectiveness and safety of endovascular treatment of visceral pseudoaneurysms using Ethylene-Vinyl Alcohol (EVOH) Copolymer-Based Non-Adhesive Liquid Embolic Agents (NALEAs). Materials and Methods: Consecutive patients who underwent endovascular embolization with EVOH-based NALEAs for visceral artery pseudoaneurysms between January 2018 and June 2023 were retrospectively evaluated. Results: 38 embolizations were performed. Technical success was achieved in all patients. The clinical success rate was high (92.1% overall), with no significant differences between ruptured and unruptured VAPs (p = 0.679). Seven patients (18.4%) experienced procedure-related complications, related to one case of non-target embolization, four splenic abscesses due to end-organ infarction, and two femoral pseudoaneurysms. The rates of procedure-related complications, end-organ infarction, and vascular access-site complications did not significantly differ between ruptured and unruptured VAPs (p > 0.05). Conclusions: Both ruptured and unruptured visceral pseudoaneurysms can be effectively and safely treated with NALEA-based endovascular embolization. We suggest considering the use of NALEAs, particularly in specific clinical cases that highlight their advantages, including patients with coagulopathy, fragile vessels, and embolization targets that are located at a considerable distance from the microcatheter tip and are otherwise difficult to reach.

The severe acute respiratory syndrome, coronavirus 2 (SARS-CoV-2), is a positive-sense single-stranded ribonucleic acid (RNA) virus contagious in humans and responsible for the ongoing coronavirus disease 2019 (COVID-19) [...]

Threshold concepts can lead to higher discipline comprehension but may also lead to the formation of educational barriers. The acceptance of evolutionary theory, a threshold concept, may be impacted by barriers associated with a student's educational, religious, psychological, and social background. The objectives of this study were to examine the efficacy of teaching evolution online and to assess how educational barriers affect the acceptance of the theory. Pre- and post-semester surveys were distributed to students in a non-science major's online evolution course at a primarily minority-serving Catholic university to evaluate potential barriers and student's Measure of Acceptance of Evolution (MATE). MATE scores increased significantly by the end of the semester, suggesting that online platforms may be effective for evolution education. Learning barriers shifted during the semester: while reported religiosity remained unchanged, it was significantly correlated with MATE scores in the pre- but not post-surveys. Psychological and science understanding barriers were also significant predictors of MATE scores in the pre-survey, whereas only psychological and social barriers were significant in the post-survey. These results suggest that religiosity need not be impacted by evolution education and barriers associated with religiosity are not insurmountable and are reduced by the exposure to evolution education.

Species interactions that can enhance habitat heterogeneity such as facilitation cascades of foundation species have been overlooked in biodiversity models. This study conducted 22 geographically distributed experiments in different ecosystems and biogeographical regions to assess the extent to which biodiversity is explained by three axes of habitat heterogeneity in facilitation cascades.