Predictors of high flow oxygen therapy failure in COVID-19-related severe hypoxemic respiratory failure

Background: During COVID-19 pandemic, people who developed pneumonia and needed supplemental oxygen, where treated with low-flow oxygen therapy systems and non-invasive methods, including oxygen therapy using high flow nasal cannula (HFNC) and the application of bi-level or continuous positive airway pressure (BiPAP or CPAP). We aimed to investigate the outcomes of critical COVID-19 patients treated with HFNC and unveil predictors of HFNC failure. // Methods: We retrospectively enrolled patients admitted to COVID-19 wards and treated with HFNC for COVID-19-related severe hypoxemic respiratory failure. The primary outcome of this study was treatment failure, such as the composite of intubation or death during hospital stay. The association between treatment failure and clinical features was evaluated using logistic regression models. // Results: One hundred thirty-two patients with a median (IQR) PaO2/FiO2 ratio 96 (63–173) mmHg at HFNC initiation were studied. Overall, 45.4% of the patients were intubated. Hospital mortality was 31.8%. Treatment failure (intubation or death) occurred in 50.75% and after adjustment for age, gender, Charlson Comorbidity index (CCI) score and National Early Warning Score 2 (NEWS2) score on admission and PaO2/FiO2 ratio and acute respiratory distress syndrome (ARDS) severity at the time of HFNO initiation, it was significantly associated with the presence of dyspnea [adjusted OR 2.48 (95% CI: 1.01–6.12)], and higher Urea serum levels [adjusted OR 1.25 (95% CI: 1.03–1.51) mg/dL]. // Conclusions: HFNC treatment was successful in almost half of the patients with severe COVID-19- related acute hypoxemic respiratory failure (AHRF). The presence of dyspnea and high serum Urea levels on admission are closely related to HFNC failure

Quadruplets and Quintuplets

A high-order pregnancy is always a challenge not only for the couple but also for the obstetrician, the pediatricians, the midwives, and the whole stuff of an obstetric clinic. The breakthroughs of infertility treatments have made more couples to postpone the birth of their children until they feel professionally and financially safe, many times after the age of 40. The advanced age of the mother puts extra pressure to the clinician for immediate success, leading to a rise of high-order pregnancies until the introduction of regulations and laws in many countries. The cost of a quadruplet and quintuplet pregnancy can be unbearable, not only financially but also psychologically. The management of such a pregnancy is also challenging since its beginning and to the end. Modern techniques and methods can also be difficult to be implemented on a quadruplet of quintuplet pregnancy because of the fear of losing four or five embryos at once. At the same time, the limited number of cases makes it almost impossible for studies to be made and guidelines to be established for most of the cases

A novel tumor suppressive role of Prox1 in breast cancer via c-myc

Breast cancer is one of the most lethal malignancies in women worldwide and is characterized by rapid growth and low survival rates, despite advances in tumor biology and therapies. Novel therapeutic approaches require new insights into the molecular mechanisms of malignant transformation and progression. To this end, here, we identified Prox1 as a negative regulator of proliferation and tumor-related metabolism in breast cancer. In particular, we showed that breast tumors from human patients exhibited reduced levels of Prox1 expression, while high expression levels of Prox1 were associated with a favorable prognosis in breast cancer patients. Moreover, we experimentally demonstrated that Prox1 was sufficient to strongly suppress proliferation, migration, and the Warburg effect in human breast cancer cells without inducing apoptosis. Most importantly, over-expression of Prox1 inhibited breast tumor growth in vivo in both heterotopic and orthotopic xenograft mouse models. The anti-tumorigenic effect of Prox1 was mediated by the direct repression of c-Myc transcription and its downstream target genes. Consistently, c-Myc over-expression from an artificial promoter that was not targeted by Prox1 reversed Prox1’s anti-tumor effects. These findings suggest that Prox1 has a tumor suppressive role via direct transcriptional regulation of c-Myc, making it a promising therapeutic gene for breast cancer.Ο καρκίνος του μαστού αποτελεί την δεύτερη βασικότερη αιτία θανάτου στις γυναίκες παγκόσμια. Παρά την πρόοδο που έχει σημειωθεί στις ιατροβιολογικές επιστήμες και τις παρεχόμενες θεραπείες, ο καρκίνος του μαστού χαρακτηρίζεται από ταχεία ανάπτυξη και χαμηλά ποσοστά επιβίωσης. Οι παρατηρήσεις αυτές υπογραμμίζουν την ανάγκη για περαιτέρω εμβάθυνση και μελέτη σχετικά με τους μοριακούς μηχανισμούς ανάπτυξης και εξέλιξης της κακοήθειας. Προς την κατεύθυνση αυτή, μελετήσαμε τον μεταγραφικό παράγοντα Prox1 ο οποίος διαδραματίζει κρίσιμο ρόλο στην καταστολή του καρκίνου του μαστού. Συγκεκριμένα, η βιοπληροφορική ανάλυση των δεδομένων γονιδιακής έκφρασης από όγκους ασθενών που βρίσκονται σε βάσεις δεδομένων, όπως το Oncomine (www.oncomine.org) και το TCGA (The Cancer Genome Atlas, www.cancergenome.nih.gov), έδειξε ότι ο Prox1 μειώνεται δραματικά στους όγκους του μαστού λόγω επιγενετικής αποσιώπησης. Επιπλέον, παρατηρήσαμε ότι το Prox1 καταστέλλει έντονα τον πολλαπλασιασμό και τη μετανάστευση των ανθρώπινων καρκινικών κυττάρων μαστού, χωρίς να προάγει την απόπτωση. Ακόμη, ενδιαφέρον εύρημα της παρούσας μελέτης ήταν η παρατήρηση ότι η υπερ-έκφραση του Prox1 οδήγησε σε μειωμένα επίπεδα γλυκόζης και γαλακτικού οξέος στο υπερκείμενο των μαστικών καρκινικών κυττάρων. Η μοριακή εμβάθυνση αυτής της παρατήρησης κατέδειξε ότι το Prox1καταστέλλει την έκφραση του γονιδίου c-Myc, καθώς και των γονιδίων που ρυθμίζονται από το c-Myc (συμπεριλαμβανομένου του Glut1, του HK2 και του PDK1, που αποτελεί βασικό ρυθμιστή της γλυκόλυσης), καθώς και την επαγωγή του MPC1, του μιτοχονδριακού μεταφορέα πυροσταφυλικού. Τα δεδομένα αυτά υποδηλώνουν ότι το Prox1 μπορεί να αναστείλει τηνικανότητα των καρκινικών κυττάρων μαστού να παράγουν ATP κυρίως μέσω της γλυκόλυσης και της παραγωγής γαλακτικού οξέος (φαινόμενο Warburg). Σε συμφωνία με τις παραπάνω παρατηρήσεις, το Prox1 καταστέλλει σημαντικά την ανάπτυξη των όγκων του μαστού in vivo σε ετεροτοπικά και ορθοτοπικά μοντέλα ξενομοσχεύματος ποντικών. Συνοπτικά, η μελέτη μας καθιερώνει το Prox1 ως παράγοντα αναστολής του όγκου μέσω της αρνητικής ρύθμισης του cMyc και της γλυκόλυσης και ως δυνητικά θεραπευτικό στόχο στον καρκίνο του μαστού

Long Non-Coding RNA Lacuna Regulates Neuronal Differentiation of Neural Stem Cells During Brain Development

Although long non-coding RNAs (lncRNAs) is one of the most abundant classes of RNAs encoded within the mammalian genome and are highly expressed in the adult brain, they remain poorly characterized and their roles in the brain development are not well understood. Here we identify the lncRNA Lacuna (also catalogued as NONMMUT071331.2 in NONCODE database) as a negative regulator of neuronal differentiation in the neural stem/progenitor cells (NSCs) during mouse brain development. In particular, we show that Lacuna is transcribed from a genomic locus near to the Tbr2/Eomes gene, a key player in the transition of intermediate progenitor cells towards the induction of neuronal differentiation. Lacuna RNA expression peaks at the developmental time window between E14.5 and E16.5, consistent with a role in neural differentiation. Overexpression experiments in ex vivo cultured NSCs from murine cortex suggest that Lacuna is sufficient to inhibit neuronal differentiation, induce the number of Nestin+ and Olig2+ cells, without affecting proliferation or apoptosis of NSCs. CRISPR/dCas9-KRAB mediated knockdown of Lacuna gene expression leads to the opposite phenotype by inducing neuronal differentiation and suppressing Nestin+ and Olig2+ cells, again without any effect on proliferation or apoptosis of NSCs. Interestingly, despite the negative action of Lacuna on neurogenesis, its knockdown inhibits Eomes transcription, implying a simultaneous, but opposite, role in facilitating the Eomes gene expression. Collectively, our observations indicate a critical function of Lacuna in the gene regulation networks that fine tune the neuronal differentiation in the mammalian NSCs

Altered SERCA Expression in Breast Cancer

Background and Objectives: Calcium (Ca2+) signaling is critical for the normal functioning of various cellular activities. However, abnormal changes in cellular Ca2+ can contribute to pathological conditions, including various types of cancer. The maintenance of intracellular Ca2+ levels is achieved through tightly regulated processes that help maintain Ca2+ homeostasis. Several types of regulatory proteins are involved in controlling intracellular Ca2+ levels, including the sarco/endoplasmic reticulum (SR/ER) Ca2+ ATPase pump (SERCA), which maintains Ca2+ levels released from the SR/ER. In total, three ATPase SR/ER Ca2+-transporting (ATP2A) 1-3 genes exist, which encode for several isoforms whose expression profiles are tissue-specific. Recently, it has become clear that abnormal SERCA expression and activity are associated with various types of cancer, including breast cancer. Breast carcinomas represent 40% of all cancer types that affect women, with a wide variety of pathological and clinical conditions. Materials and methods: Using cBioPortal breast cancer patient data, Kaplan–Meier plots demonstrated that high ATP2A1 and ATP2A3 expression was associated with reduced patient survival. Results: The present study found significantly different SERCA specific-type expressions in a series of breast cancer cell lines. Moreover, bioinformatics analysis indicated that ATP2A1 and ATP2A3 expression was highly altered in patients with breast cancer. Conclusion: Overall, the present data suggest that SERCA gene-specific expressioncan possibly be considered as a crucial target for the control of breast cancer development and progression

Absorption coefficients and scattering losses of TGG, TGP, KTF, FS, and CeF₃ magneto-optic crystals in the visible via cavity ring down spectroscopy

We demonstrate a method for determining small absorption coefficients and surface scattering losses of crystals using cavity ring down spectroscopy, and perform measurements on crystals of TGG, TGP, FS, KTF, and CeF₃, at 532nm and 634nm. We separate the surface-scattering and absorption losses by using crystals of different length. The measurements differ from those in the literature, especially for small absorption coefficients. We define a figure of merit (FoM) for magneto-optic crystals in signal-reversing cavity-ringdown polarimetry, which depends on the cavity losses, and on the crystal Verdet constant and absorption coefficient, and use it to evaluate the crystals for suitability for intra-cavity applications. We show that TGP has a significantly higher FoM compared to the other crystals, for crystal lengths up to 16 mm, whereas CeF₃ and FS outperform TGP for longer crystals

Capture reaction cross-section measurements relevant to p process: the case of (α , γ) reactions on 63Cu, 72Ge,118Sn and the 107Ag(ρ, γ)108Cd reaction

The cross sections of the 72Ge( α , γ)76Se and 1°7Ag(ρ, γ)1°8Cd reactions were measured at energies relevant to p-process nucleosynthesis. The new data, together with cross section results from our previous ( α , γ) measure-ments on 65Cu and 118Sn and other ( α , γ) cross-section data reported in lit-erature are compared with statistical model calculations performed using the latest version (1.9) of the statistical model code TALYS. In addition, the effect on these calculations of different combinations of the optical model potentials (OMPs), nuclear level densities (NLDs) and γ-ray strength functions (γSFs) entering the calculations was investigated

Capture reaction cross-section measurements relevant to p process: the case of (α , γ) reactions on

The cross sections of the 72Ge( α , γ)76Se and 1°7Ag(ρ, γ)1°8Cd reactions were measured at energies relevant to p-process nucleosynthesis. The new data, together with cross section results from our previous ( α , γ) measure-ments on 65Cu and 118Sn and other ( α , γ) cross-section data reported in lit-erature are compared with statistical model calculations performed using the latest version (1.9) of the statistical model code TALYS. In addition, the effect on these calculations of different combinations of the optical model potentials (OMPs), nuclear level densities (NLDs) and γ-ray strength functions (γSFs) entering the calculations was investigated

EPHA2, EPHA4, and EPHA7 Expression in Triple-Negative Breast Cancer

Ongoing research continues to elucidate the complex role of ephrin receptors (EPHs) and their ligands (ephrins) in breast cancer pathogenesis, with their varying expression patterns implied to have an important impact on patients’ outcome. The current study aims to investigate the clinical significance of EPHA2, EPHA4, and EPHA7 expression in triple-negative breast cancer (TNBC) cases. EPHA2, EPHA4, and EPHA7 protein expression was assessed immunohistochemically on formalin-fixed and paraffin-embedded (FFPE) TNBC tissue sections from 52 TNBC patients and correlated with key clinicopathologic parameters and patients’ survival data (overall survival (OS); disease-free survival (DFS)). EPHA2, EPHA4, and EPHA7 expression was further examined in TNBC cell lines. EPHA2 overexpression was observed in 26 (50%) of the TNBC cases, who exhibited a shorter OS and DFS than their low-expression counterparts, with EPHA2 representing an independent prognostic factor for OS and DFS (p = 0.0041 and p = 0.0232, respectively). EPHA4 overexpression was associated with lymph node metastasis in TNBC patients (p = 0.0546). Alterations in EPHA2, EPHA4, and EPHA7 expression levels were also noted in the examined TNBC cell lines. Our study stresses that EPHA2 expression constitutes a potential prognostic factor for TNBC patients. Given the limited treatment options and poorer outcome that accompany the TNBC subtype, EPHA2 could also pose as a target for novel, more personalized, and effective therapeutic approaches for those patients