Miracle-dz/UniFAR-FTUs huggingface dataset:
Decitabine combined with all-trans retinoic acid as treatment in a case of primary myelofibrosis transforming into acute myeloid leukaemia

Primary myelofibrosis (PMF) is a type of cloned myeloproliferative neoplasm stemming from haematopoietic stem cells, and tends to transform to acute myeloid leukaemia (AML) in approximately 10–20% of cases over a 10-year period. The transformation into AML has a poor prognosis, with a median overall survival of only 2.6 months in patients receiving supportive treatment. To date, treatment of AML transformation remains poor. The case of a 58-year-old female patient with AML transformed from PMF, who was treated with decitabine combined with all-trans retinoic acid, is reported. The patient had complete remission and a 17-month overall survival from initial diagnosis of transformed AML, with tolerated haematologic toxicity during the treatment period.
Florida clade 1 equine influenza virus in France

Preliminary results from a large scale seroepidemiological study we conducted in 2018, involving 3000 French horses, reveals that equine influenza vaccination is well established, with 90 per cent of the studied population possessing antibody titres above the protection threshold against clinical signs of disease and 60 per cent virus shedding.1 The predominant use in France of the recombinant canarypox virus equine influenza vaccine ProteqFlu-Te (Boehringer Ingelheim/Merial), the only fully updated equine influenza vaccine licensed in the EU with DIVA (differentiating infected from vaccinated animal) capability, allowed us to confirm that the measured equine influenza immunological status was mostly attributed to equine influenza vaccination, with little immunological …
A Phase 2 Randomized, Sham-Controlled Trial of Internal Carotid Artery Infusion of Autologous Bone Marrow–Derived ALD-401 Cells in Patients With Recent Stable Ischemic Stroke (RECOVER-Stroke)

Background: Ischemic stroke has no approved treatments to enhance recovery. ALD-401 is an enriched population of aldehyde dehydrogenase-bright stem cells, capable of reducing neurological deficits in animal models. The primary objective of this trial was to determine the safety of internal carotid artery, intra-arterially delivered autologous bone marrow–derived ALD-401 in patients with disabling middle cerebral artery stroke in comparison with sham harvest with sham infusion. Secondary objectives were to determine feasibility and efficacy. Methods: This was a prospective phase 2, industry-funded, randomized, sham-controlled, parallel-group, multicenter study with blinded assessments. One hundred subjects were planned, aged 30 to 83 years, with confirmed first-time middle cerebral artery ischemic stroke with modified Rankin scale ≥3. Study patients were randomly assigned 3:2 to bone marrow harvest at 11 to 17 days after stroke followed 2 days later by intracarotid infusion of ALD-401 versus sham harvest and then sham infusion in the same timeframe. The primary study outcome was safety based on the incidence of a 4-point National Institutes of Health Stroke Scale worsening and the proportion of serious adverse events. Efficacy was based on modified Rankin scale change at 90 days. Other secondary outcomes were the proportions of patients experiencing adverse events, disability by Barthel Index, quality of life using EQ-5D, rehabilitation utilization, disability at 1 year, and MRI evidence of complications. Results: There were no infusional or allergic reactions and no difference in treatment emergent adverse events. Four patients had small areas of asymptomatic restricted diffusion on MRI in the treatment group. There was no significant difference between the ALD-401 and placebo groups on the modified Rankin scale for the intent-to-treat population at day 90 (mean difference, 0.3; 95% CI, –0.3 to 0.8; P=0.330). There were no significant differences between the groups on any of the secondary efficacy measures. Conclusions: Intracarotid infusion of ALD-401 does not lead to clinical adverse events in patients with subacute ischemic stroke, although there was a higher incidence of small lesions on MRI in the treatment group. There was no difference in the primary efficacy end point between the groups. The study provides a framework for the design and conduct of future intra-arterial cell therapy trials in stroke. Clinical Trial Registration: URL: https://www.clinicaltrials. gov. Unique identifier: NCT01273337.
Metabolomics and Age-Related Macular Degeneration

Age-related macular degeneration (AMD) leads to irreversible visual loss, therefore, early intervention is desirable, but due to its multifactorial nature, diagnosis of early disease might be challenging. Identification of early markers for disease development and progression is key for disease diagnosis. Suitable biomarkers can potentially provide opportunities for clinical intervention at a stage of the disease when irreversible changes are yet to take place. One of the most metabolically active tissues in the human body is the retina, making the use of hypothesis-free techniques, like metabolomics, to measure molecular changes in AMD appealing. Indeed, there is increasing evidence that metabolic dysfunction has an important role in the development and progression of AMD. Therefore, metabolomics appears to be an appropriate platform to investigate disease-associated biomarkers. In this review, we explored what is known about metabolic changes in the retina, in conjunction with the emerging literature in AMD metabolomics research. Methods for metabolic biomarker identification in the eye have also been discussed, including the use of tears, vitreous, and aqueous humor, as well as imaging methods, like fluorescence lifetime imaging, that could be translated into a clinical diagnostic tool with molecular level resolution.
Engaging Gypsy, Roma, and Traveller Communities in Research: Maximizing Opportunities and Overcoming Challenges

Gypsy, Roma, and Traveller people are marginalized worldwide and experience severe health inequalities, even in comparison to other ethnic minority groups. While diverse and hard to categorize, these communities are highly cohesive and members have a strong sense of identity as a group apart from the majority population. Researchers commonly experience challenges in accessing, recruiting, and retaining research participants from these communities, linked to their outsider status, insular nature, and history of discrimination. In this article, the challenges and the opportunities of engaging Gypsies, Roma, and Travellers in a multicenter qualitative research project are discussed. The management of public involvement and community engagement in this U.K.-based project provides insights into conducting research effectively with ethnically and linguistically diverse communities, often considered to be “hard to reach. ”
Periprostatic Adipose Tissue Favors Prostate Cancer Cell Invasion in an Obesity-Dependent Manner: Role of Oxidative Stress

Prostate gland is surrounded by periprostatic adipose tissue (PPAT), which is increasingly believed to play a paracrine role in prostate cancer progression. Our previous work demonstrates that adipocytes promote homing of prostate cancer cells to PPAT and that this effect is upregulated by obesity. Here, we show that once tumor cells have invaded PPAT (mimicked by an in vitro model of coculture), they establish a bidirectional crosstalk with adipocytes, which promotes tumor cell invasion. Indeed, tumor cells induce adipocyte lipolysis and the free fatty acids (FFA) released are taken up and stored by tumor cells. Incubation with exogenous lipids also stimulates tumor cell invasion, underlining the importance of lipid transfer in prostate cancer aggressiveness. Transferred FFAs (after coculture or exogenous lipid treatment) stimulate the expression of one isoform of the pro-oxidant enzyme NADPH oxidase, NOX5. NOX5 increases intracellular reactive oxygen species (ROS) that, in turn, activate a HIF1/MMP14 pathway, which is responsible for the increased tumor cell invasion. In obesity, tumor-surrounding adipocytes are more prone to activate the depicted signaling pathway and to induce tumor invasion. Finally, the expression of NOX5 and MMP14 is upregulated at the invasive front of human tumors where cancer cells are in close proximity to adipocytes and this process is amplified in obese patients, underlining the clinical relevance of our results. Implications: Our work emphasizes the key role of adjacent PPAT in prostate cancer dissemination and proposes new molecular targets for the treatment of obese patients exhibiting aggressive diseases.
Symptoms that are associated with decreased pancreatic enzyme flow: MRCP assessment

Pancreatic exocrine insufficiency is one of the causes of malabsorption syndrome. In many cases of malabsorption syndrome, pancreatic exocrine insufficiency can be treated with pancreatic enzyme replacement therapy. Therefore, it is important to detect pancreatic endocrine insufficiency as early and accurately as possible. Recent studies have shown that cine‐dynamic MR cholangiopancreatography (MRCP) may be useful to evaluate pancreatic exocrine function
Vaskuläre Biomarker der retinalen Gefäßanalyse

Zusammenfassung Mit modernen nicht invasiven bildgebenden Verfahren lassen sich anhand der Fundusfotografie bzw. der optischen Verfilmung Aspekte der funktionellen und strukturellen retinalen Gefäßveränderungen objektiv untersuchen. Der Zustand und das Verhalten retinaler Gefäße beeinflussen im prä-, post- und kapillaren Bereich den Blutfluss und strömungsbedingte Stoffwechselverhältnisse passiv und aktiv über den Gefäßdurchmesser. Retinale Gefäße gleichen von Aufbau und Funktion den zerebralen Gefäßen und spiegeln den Zustand der Mikrozirkulation wider. Mithilfe von aus den Gefäßweiten berechneten Biomarkern soll eine Aussage über die Prognose von systemischen vaskulär bedingten Erkrankungen getroffen werden. Die statische retinale Gefäßanalyse befasst sich mit der Untersuchung des Zustandes der prä- und postkapillaren Gefäßdurchmesser der retinalen Mikrozirkulation anhand einer optischen Fundusaufnahme. Bei der dynamischen retinalen Gefäßanalyse wird der Längsschnitt eines retinalen Gefäßes nicht invasiv funktionell und strukturell über einen Zeitraum vor, während und nach einer spezifischen vaskulären Stimulation untersucht. Die genaue Methodologie der Auswertung und die Bezeichnung der Parameter variieren bei unterschiedlichen Ansätzen. Mittels retinaler Gefäßanalyse wurden bislang mehrere klinische Querschnitts- und Interventionsstudien in der Augenheilkunde und anderen Fachgebieten, inkl. Kardiologie, Neurologie, Neurochirurgie, Nephrologie, Gynäkologie, Sportmedizin, Diabetologie, Hypertensiologie usw. durchgeführt. Mit der statischen retinalen Gefäßanalyse steht eine kostengünstige, reproduzierbare, nicht invasive Screeningtechnik zur Verfügung, um eine prognostische Aussage über die Gefäßgesundheit eines individuellen Patienten zu treffen. Die dynamische retinale Gefäßanalyse besitzt ein weiteres diagnostisches Anwendungsspektrum als die statische, da sie das Verhalten retinaler Gefäße zeitkontinuierlich untersucht. Die Evaluation vaskulärer Erkrankungen sowie zerebro- bzw. kardiovaskulärer Morbidität und Mortalität mittels mehrerer methodologischer Modalitäten retinaler Gefäßanalyse mit ihren jeweiligen quantitativen Biomarkern bietet eine zukunftsträchtige diagnostische Perspektive. Die interdisziplinäre klinische Anwendung dieser vaskulären Biomarker gewinnt zunehmend an Bedeutung, sowohl in der Augenheilkunde als auch in anderen Fachgebieten.
Reconstruction of 3d neuronal structures from densely packed electron microscopy data stacks

The goal of fully decoding how the brain works requires a detailed wiring diagram of the brain network that reveals the complete connectivity matrix. Recent advances in high-throughput 3D electron microscopy (EM) image acquisition techniques have made it possible to obtain high-resolution 3D imaging data that allows researchers to follow axons and dendrites and to identify pre-synaptic and post-synaptic sites, enabling the reconstruction of detailed neural circuits of the nervous system at the level of synapses. However, these massive data sets pose unique challenges to structural reconstruction because the inevitable staining noise, incomplete boundaries, and inhomogeneous staining intensities increase difficulty of 3D reconstruction and visualization. In this dissertation, a new set of algorithms are provided for reconstruction of neuronal morphology from stacks of serial EM images. These algorithms include (1) segmentation algorithms for obtaining the full geometry of neural circuits, (2) interactive segmentation tools for manual correction of erroneous segmentations, and (3) a validation method for obtaining a topologically correct segmentation when a set of segmentation alternatives are available. Experimental results obtained by using EM images containing densely packed cells demonstrate that (1) the proposed segmentation methods can successfully reconstruct full anatomical structures from EM images, (2) the editing tools provide a way for the user to easily and quickly refine incorrect segmentations, (3) and the validation method is effective in combining multiple segmentation results. The algorithms presented in this dissertation are expected to contribute to the reconstruction of the connectome and to open new directions in the development of reconstruction methods.
YpdA, a putative bacillithiol disulfide reductase, contributes to cellular redox homeostasis and virulence in Staphylococcus aureus

The intracellular redox environment of Staphylococcus aureus is mainly buffered by bacillithiol (BSH), a low molecular weight thiol. The identity of enzymes responsible for the recycling of oxidized bacillithiol disulfide (BSSB) to the reduced form (BSH) remains elusive. We examined YpdA, a putative bacillithiol reductase, for its role in maintaining intracellular redox homeostasis. The ypdA mutant showed increased levels of BSSB and a lower bacillithiol redox ratio vs. the isogenic parent, indicating a higher level of oxidative stress within the bacterial cytosol. We showed that YpdA consumed NAD(P)H; and YpdA protein levels were augmented in response to stress. Wild type strains overexpressing YpdA showed increased tolerance to oxidants and electrophilic agents. Importantly, YpdA overexpression in the parental strain caused an increase in BSH levels accompanied by a decrease in BSSB concentration in the presence of stress, resulting in an increase in bacillithiol redox ratio vs. the vector control. Additionally, the ypdA mutant exhibited decreased survival in human neutrophils (PMNs) as compared with the parent, while YpdA overexpression protected the resulting strain from oxidative stress in vitro and from killing by human neutrophils ex vivo. Taken together, these data present a new role for YpdA in S. aureus physiology and virulence through the bacillithiol system.
How to match bilingual tweets

In this paper, we propose a method that aligns comparable bilingual tweets which, not only takes into account the specificity of a Tweet, but treats also proper names, dates and numbers in two different languages. This permits to retrieve more relevant target tweets. The process of matching proper names between Arabic and English is a difficult task, because these two languages use different scripts. For that, we used an approach which projects the sounds of an English proper name into Arabic and aligns it with the most appropriate proper name. We evaluated the method with a classical measure and compared it to the one we developed. The experiments have been achieved on two parallel corpora and shows that our measure outperforms the baseline by 5.6% at R@1 recall.
Cenpj Regulates Cilia Disassembly and Neurogenesis in the Developing Mouse Cortex

Primary cilia are microtubule-based protuberances that project from the eukaryotic cell body to sense the extracellular environment. Ciliogenesis is closely correlated to the cell cycle and defects of cilia are related to human systemic diseases such as primary ciliary dyskinesia. However, the role of ciliogenesis in cortical development remains unclear. Here, we demonstrate that Cenpj, a protein that is required for centriole biogenesis, plays a role in regulating cilium disassembly in vivo. Depletion of Cenpj in neural progenitor cells results in long cilia and abnormal cilia disassembly. Radial glial cells Cenpj depletion exhibit uncompleted cell division, reduced cell proliferation, and increased cell apoptosis in the developing mouse cerebrum cortex, leading to microcephaly. In addition, Cenpj depletion causes long and thin primary cilia and motile cilia in adult neural stem cells and reduced cell proliferation in the subventricular zone. Furthermore, we show that Cenpj regulates cilia disassembly and neurogenesis through Kif2a, a plus-end-directed motor protein. These data collected from mice of both sexes provide insights into how ciliogenesis plays roles in cortical development and how primary microcephaly is induced by Cenpj mutations in humans. SIGNIFICANCE STATEMENT Autosomal recessive primary microcephaly is a neurodevelopmental disorder with the major symptoms of reduction of circumference of the head, brain volume, and cortex thickness with normal brain architecture in birth. We used conditional Cenpj deletion mice and found that neural progenitor cells (NPCs) exhibited long primary cilia and abnormal cilium appendages. The defective cilium disassembly caused by Cenpj depletion might correlate to reduced cell proliferation, uncompleted cell division, cell apoptosis, and microcephaly in mice. Cenpj also regulates the cilium structure of adult neural stem cells and adult neurogenesis in mice. Additionally, our results illustrate that Cenpj regulates cilia disassembly and neurogenesis through Kif2a, indicating that primary cilia dynamics play a crucial role in NPC mitosis and adult neurogenesis.
Sensitive ADAR editing reporter in cancer cells enables high-throughput screening of small molecule libraries

Adenosine to inosine editing is common in the human transcriptome and changes of this essential activity is associated with disease. Children with ADAR1 mutations develop fatal Aicardi-Goutières syndrome characterized by aberrant interferon expression. In contrast, ADAR1 overexpression is associated with increased malignancy of breast, lung and liver cancer. ADAR1 silencing in breast cancer cells leads to increased apoptosis, suggesting an anti-apoptotic function that promotes cancer progression. Yet, suitable high-throughput editing assays are needed to efficiently screen chemical libraries for modifiers of ADAR1 activity. We describe the development of a bioluminescent reporter system that facilitates rapid and accurate determination of endogenous editing activity. The system is based on the highly sensitive and quantitative Nanoluciferase that is conditionally expressed upon reporter-transcript editing. Stably introduced into cancer cell lines, the system reports on elevated endogenous ADAR1 editing activity induced by interferon as well as knockdown of ADAR1 and ADAR2. In a single-well setup we used the reporter in HeLa cells to screen a small molecule library of 33 000 compounds. This yielded a primary hit rate of 0.9% at 70% inhibition of editing. Thus, we provide a key tool for high-throughput identification of modifiers of A-to-I editing activity in cancer cells.
Il questionario HIT (How I Think) per la misurazione delle distorsioni cognitive che favoriscono il comportamento antisociale. Una validazione su 1688 studenti italiani

La ricerca si propone di contribuire alla validazione italiana del questionario How I think (HIT) di Barriga et al. (2001). Lo strumento rileva le Distorsioni cognitive a favore del se (Self serving cognitive biases) che facilitano i comportamenti antisociali. Le distorsioni sono cosi denominate: Autocentrazione (Self -Centered); Incolpare gli altri (Blaming Others); Minimizzare/Dare nomi sbagliati (Minimizing/Mislabelling); Assumere il Peggio (Assuming the Worst). Parte di queste distorsioni corrispondono ad alcuni dei meccanismi di disimpegno morale descritti da Bandura, Caprara e collaboratori (ad esempio Bandura, et al., 1996), e, prima ancora, alle tecniche di neutralizzazione identificate da Sykes e Matza (1957). Cio che contraddistingue lo HIT e il ruolo di primo piano attribuito all’Autocentrazione (distorsione non menzionata dai precedenti autori) e la sua connessione con una teoria dello sviluppo morale. Lo strumento e stato somministrato a un campione di 1688 studenti italiani, provenienti da regioni del Nord e del Sud Italia, frequentanti le diverse classi della scuole secondaria. Ad un sottocampione di 285 ragazzi sono stati somministrati anche la scala DMC (Caprara et al., 2006) e il questionario sui valori di Schwartz (1992). Ad un sottocampione di 587 ragazzi, di I, III, e V sono state somministrate la scala sulla disapprovazione della devianza e quella sulla devianza dichiarata, contenute nel questionario "Io e la mia salute" (Bonino et al., 2003). L’analisi fattoriale confermativa ha identificato i fattori corrispondenti alle quattro distorsioni. La validita convergente dello strumento e stata confermata dalle elevate correlazioni positive tra i punteggi fattoriali corrispondenti alle quattro distorsioni cognitive e lo DMC (0,68 < r < 0,70) i comportamenti devianti dichiarati (0,58 < r < 0,59) e dalla correlazione negativa con la disapprovazione dei comportamenti devianti (-0,58 < r < -0,68). Per quanto riguarda i valori, sono emerse correlazioni positive con potere (0,35 < r < 0,40), edonismo (0,28 < r < 0,31) stimolazione (0,27 < r < 0,31) e successo (0,15 < r < 0,17) e negative con benevolenza (-0,18 < r < -0,20) e universalismo (tutti gli r = -0,20), conformismo (-0,21 < r < -0,28) e spiritualita (-0,16 < r < -0,17). Un’interessante relazione curvilinea tra l’eta dei partecipanti e le prestazioni nelle diverse scale dei comportamenti antisociali viene infine descritta e interpretata.
Influence of physico-chemical characteristics of sediment on the in situ spatial distribution of F-specific RNA phages in the riverbed

&NA; Riverbed sediment is commonly described as an enteric virus reservoir and thought to play an important role in water column contamination, especially during rainfall events. Although the occurrence and fate of faecal‐derived viruses are fairly well characterized in water, little information is available on their presence as their interactions with sediment. This study aimed at determining the main environmental factors responsible for the presence of enteric viruses in riverbed sediment. Using a combination of microbiological and physico‐chemical analyses of freshly field‐sampled sediments, we demonstrated their contamination by faecal phages. The in situ spatial distribution of phages in sediment was mainly driven by sediment composition. A preferential phage accumulation occurred along one bank of the river, where the quantity of fine sands and clay particles smaller than 0.2 mm was the highest. Additionally, a mineralogical analysis revealed the influence of the heterogeneous presence of virus sorbents such as quartz, calcite, carbonates and iron‐bearing phases (goethite) on the phage spatial pattern. A more precise knowledge of the composition of riverbed sediment is therefore useful for predicting preferential areas of enteric virus accumulation and should allow more accurate microbial risk assessment when using surface water for drinking water production or recreational activities. &NA; Graphical Abstract Figure. The heterogeneous presence of fine sands, clays and iron‐bearing phases has an influence on the in situ spatial distribution of faecal phages in riverbed sediment.