Showing papers by "Ben-Gurion University of the Negev published in 2022"

Placental Tissue Destruction and Insufficiency From COVID-19 Causes Stillbirth and Neonatal Death From Hypoxic-Ischemic Injury

Abstract: Perinatal death is an increasingly important problem as the coronavirus disease 2019 (COVID-19) pandemic continues, but the mechanism of death has been unclear.To evaluate the role of the placenta in causing stillbirth and neonatal death following maternal infection with COVID-19 and confirmed placental positivity for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2).Case-based retrospective clinicopathologic analysis by a multinational group of 44 perinatal specialists from 12 countries of placental and autopsy pathology findings from 64 stillborns and 4 neonatal deaths having placentas testing positive for SARS-CoV-2 following delivery to mothers with COVID-19.Of the 3 findings constituting SARS-CoV-2 placentitis, all 68 placentas had increased fibrin deposition and villous trophoblast necrosis and 66 had chronic histiocytic intervillositis. Sixty-three placentas had massive perivillous fibrin deposition. Severe destructive placental disease from SARS-CoV-2 placentitis averaged 77.7% tissue involvement. Other findings included multiple intervillous thrombi (37%; 25 of 68) and chronic villitis (32%; 22 of 68). The majority (19; 63%) of the 30 autopsies revealed no significant fetal abnormalities except for intrauterine hypoxia and asphyxia. Among all 68 cases, SARS-CoV-2 was detected from a body specimen in 16 of 28 cases tested, most frequently from nasopharyngeal swabs. Four autopsied stillborns had SARS-CoV-2 identified in internal organs.The pathology abnormalities composing SARS-CoV-2 placentitis cause widespread and severe placental destruction resulting in placental malperfusion and insufficiency. In these cases, intrauterine and perinatal death likely results directly from placental insufficiency and fetal hypoxic-ischemic injury. There was no evidence that SARS-CoV-2 involvement of the fetus had a role in causing these deaths.

Quantum computational complexity from quantum information to black holes and back

Abstract: Quantum computational complexity estimates the difficulty of constructing quantum states from elementary operations, a problem of prime importance for quantum computation. Surprisingly, this quantity can also serve to study a completely different physical problem - that of information processing inside black holes. Quantum computational complexity was suggested as a new entry in the holographic dictionary, which extends the connection between geometry and information and resolves the puzzle of why black hole interiors keep growing for a very long time. In this pedagogical review, we present the geometric approach to complexity advocated by Nielsen and show how it can be used to define complexity for generic quantum systems; in particular, we focus on Gaussian states in QFT, both pure and mixed, and on certain classes of CFT states. We then present the conjectured relation to gravitational quantities within the holographic correspondence and discuss several examples in which different versions of the conjectures have been tested. We highlight the relation between complexity, chaos and scrambling in chaotic systems. We conclude with a discussion of open problems and future directions. This article was written for the special issue of EPJ-C Frontiers in Holographic Duality.

Regressing SARS-CoV-2 Sewage Measurements Onto COVID-19 Burden in the Population: A Proof-of-Concept for Quantitative Environmental Surveillance

Abstract: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is an RNA virus, a member of the coronavirus family of respiratory viruses that includes severe acute respiratory syndrome coronavirus 1 (SARS-CoV-1) and the Middle East respiratory syndrome (MERS). It has had an acute and dramatic impact on health care systems, economies, and societies of affected countries during the past 8 months. Widespread testing and tracing efforts are being employed in many countries in attempts to contain and mitigate this pandemic. Recent data has indicated that fecal shedding of SARS-CoV-2 is common and that the virus RNA can be detected in wastewater. This indicates that wastewater monitoring may provide a potentially efficient tool for the epidemiological surveillance of SARS-CoV-2 infection in large populations at relevant scales. In particular, this provides important means of (i) estimating the extent of outbreaks and their spatial distributions, based primarily on in-sewer measurements, (ii) managing the early-warning system quantitatively and efficiently, and (iii) verifying disease elimination. Here we report different virus concentration methods using polyethylene glycol (PEG), alum, or filtration techniques as well as different RNA extraction methodologies, providing important insights regarding the detection of SARS-CoV-2 RNA in sewage. Virus RNA particles were detected in wastewater in several geographic locations in Israel. In addition, a correlation of virus RNA concentration to morbidity was detected in Bnei-Barak city during April 2020. This study presents a proof of concept for the use of direct raw sewage-associated virus data, during the pandemic in the country as a potential epidemiological tool.

Holographic complexity and de Sitter space

Abstract: A bstract We compute the length of spacelike geodesics anchored at opposite sides of certain double-sided flow geometries in two dimensions. These geometries are asymptotically anti-de Sitter but they admit either a de Sitter or a black hole event horizon in the interior. While in the geometries with black hole horizons, the geodesic length always exhibit linear growth at late times, in the flow geometries with de Sitter horizons, geodesics with finite length only exist for short times of the order of the inverse temperature and they do not exhibit linear growth. We comment on the implications of these results towards understanding the holographic proposal for quantum complexity and the holographic nature of the de Sitter horizon.

W Doping in Ni12P5 as a Platform to Enhance Overall Electrochemical Water Splitting.

Abstract: Bifunctional electrocatalysts for efficient hydrogen generation from water splitting must overcome both the sluggish water dissociation step of the alkaline hydrogen evolution half-reaction (HER) and the kinetic barrier of the anodic oxygen evolution half-reaction (OER). Nickel phosphides are a promising catalysts family and are known to develop a thin active layer of oxidized Ni in an alkaline medium. Here, Ni12P5 was recognized as a suitable platform for the electrochemical production of γ-NiOOH─a particularly active phase─because of its matching crystallographic structure. The incorporation of tungsten by doping produces additional surface roughness, increases the electrochemical surface area (ESCA), and reduces the energy barrier for electron-coupled water dissociation (the Volmer step for the formation of Hads). When serving as both the anode and cathode, the 15% W-Ni12P5 catalyst provides an overall water splitting current density of 10 mA cm-2 at a cell voltage of only 1.73 V with good durability, making it a promising bifunctional catalyst for practical water electrolysis.

Tracking social media during the COVID-19 pandemic: The case study of lockdown in New York State

Abstract: Facing the COVID-19 pandemic, governments have implemented a wide range of policies to contain the spread of the virus. During the pandemic, large amounts of COVID-19-related tweets emerge every day. Real-time processing of daily tweets may offer insights for monitoring public opinion about intervention measures implemented. In this work, lockdown policy in New York State has been set as a target of public opinion research. This task includes two stages, stance detection and opinion monitoring. For the stance detection stage, we explored several combinations of different text representations and classification algorithms, finding that the combination of Long Short-Term Memory (LSTM) with Global Vectors for Word Representation (GloVe) outperforms others. Due to the shortage of labeled data, we adopted the data distillation method for the training data augmentation. The augmentation of the training data allows to improve the performance of the model with a very small amount of manually-labeled data. After applying the distillation method, the accuracy of the model has been significantly improved. Utilizing the enhanced model, automatically classified tweets are analyzed over time to monitor the public opinion. By exploring the tweets in New York from January 22nd until September 30th, 2020, we show the correlation of public opinion with COVID-19 cases and mortality data, and the effect of government responses on the opinion shift. These results demonstrate the capability of the presented method to effectively and efficiently monitor public opinion during a pandemic.

Synthesis of Refractory High-Entropy Alloy WTaMoNbV by Powder Bed Fusion Process Using Mixed Elemental Alloying Powder

Abstract: The growing interest in refractory high-entropy alloys (HEAs) in the last decade is mainly due to their thermal stability, outstanding mechanical properties, and excellent corrosion resistance. However, currently HEAs are still not considered for use as common structural materials due to their inherent drawbacks in terms of processing and machining operations. The recent progress witnessed in additive manufacturing (AM) technologies has raised the option of producing complex components made of HEAs with minimal machining processes. So far, this could be achieved by using pre-alloyed powders of HEAs that were mainly produced by a conventional arc melting furnace (AMF) in the form of small compounds that were transformed into powder via a gas atomization process. To significantly reduce the production cost, the present study aims to analyze the ability to synthesize HEA WTaMoNbV via a laser powder bed fusion (LPBF) process using mixed elemental alloying powder as the raw material. For comparison, a counterpart alloy with the same chemical composition was analyzed and produced by an AMF process. The microstructures of the tested alloys were examined by scanning electron microscopy (SEM), transmission electron microscopy (TEM) and X-ray diffraction (XRD) analyses. The physical properties were evaluated in terms of density and mechanical strength, while the electrochemical behavior was assessed by potentiodynamic polarization analysis. The results disclosed similarities in microstructure, physical properties and electrochemical behavior between HEA WTaMoNbV manufactured by the proposed LPBF process and its counterpart alloy produced by an AMF process.

Secondary Organizing Pneumonia After Recovery of Mild COVID-19 Infection

Abstract: A 36-year-old male with diffuse large B-cell lymphoma on maintenance rituximab therapy presented to the emergency department with high fever and fatigue. A chest X-ray showed a lobar infiltrate, 40 days before admission the patient suffered from a mild coronavirus disease 2019 (COVID-19) infection and fully recovered. PCR nasopharyngeal swab was negative for COVID-19. Comprehensive biochemical, radiological, and pathological evaluation including 18-fluorodeoxyglucose positron emission tomography with computed tomography and transbronchial lung biopsy found no pathogen or lymphoma recurrence. Treatment for pneumonia with antibiotic and antifungal agents was nonbeneficial. A diagnosis of secondary organizing pneumonia (OP) was made after pneumonia migration and a rapid response to corticosteroids. OP secondary to a viral respiratory infection has been well described. Raising awareness for post-COVID-19 OP has therapeutic and prognostic importance because those patients benefit from steroid therapy. We believe the condition described here is underdiagnosed and undertreated by doctors worldwide. Because of the ongoing global pandemic we are now encountering a new kind of patient, patients that have recovered from COVID-19. We hope that this case may contribute to gaining more knowledge about this growing patient population.

Hospitalized Patients With Severe Coronavirus Disease 2019 During the Omicron Wave in Israel: Benefits of a Fourth Vaccine Dose

Abstract: Waning immunity and an increased incidence of coronavirus disease 2019 (COVID-19) during the Omicron outbreak led the Israeli Ministry of Health to recommend a fourth vaccine dose for high-risk individuals. In this study, we assessed its effect for hospitalized patients with severe breakthrough COVID-19.In this multicenter cohort study of hospitalized adults with severe COVID-19 in Israel, from 15 to 31 January 2022, cases were divided according to the number of vaccinations received. Poor outcome was defined as mechanical ventilation or in-hospital death and was compared between 3- and 4-dose vaccinees using logistic regression.Included were 1049 patients, median age 80 years. Among them, 394 were unvaccinated, 386 and 88 had received 3 or 4 doses, respectively. The 3-dose group was older, included more males, and immunosuppressed patients but with similar outcomes, 49% vs 51% compared with unvaccinated patients (P = .72). Patients who received 4 doses were similarly older and immunosuppressed but had better outcomes compared with unvaccinated patients, 34% vs 51% (P < .01). We examined independent predictors for poor outcome in patients who received either 3 or 4 doses a median of 161 days or 14 days before diagnosis, respectively. Receipt of the fourth dose was associated with protection (odds ratio, 0.51; 95% confidence interval, .3-.87), as was remdesivir. Male sex, chronic renal failure, and dementia were associated with poor outcomes.Among hospitalized patients with severe breakthrough COVID-19, a recent fourth dose was associated with significant protection against mechanical ventilation or death compared with 3 doses.

MEK1/2 inhibition transiently alters the tumor immune microenvironment to enhance immunotherapy efficacy against head and neck cancer

Abstract: Although the mitogen-activated protein kinases (MAPK) pathway is hyperactive in head and neck cancer (HNC), inhibition of MEK1/2 in HNC patients has not shown clinically meaningful activity. Therefore, we aimed to characterize the effect of MEK1/2 inhibition on the tumor microenvironment (TME) of MAPK-driven HNC, elucidate tumor-host interaction mechanisms facilitating immune escape on treatment, and apply rationale-based therapy combination immunotherapy and MEK1/2 inhibitor to induce tumor clearance.Mouse syngeneic tumors and xenografts experiments were used to analyze tumor growth in vivo. Single-cell cytometry by time of flight, flow cytometry, and tissue stainings were used to profile the TME in response to trametinib (MEK1/2 inhibitor). Co-culture of myeloid-derived suppressor cells (MDSC) with CD8+ T cells was used to measure immune suppression. Overexpression of colony-stimulating factor-1 (CSF-1) in tumor cells was used to show the effect of tumor-derived CSF-1 on sensitivity to trametinib and anti-programmed death- 1 (αPD-1) in mice. In HNC patients, the ratio between CSF-1 and CD8A was measured to test the association with clinical benefit to αPD-1 and αPD-L1 treatment.Using preclinical HNC models, we demonstrated that treatment with trametinib delays HNC initiation and progression by reducing tumor cell proliferation and enhancing the antitumor immunity of CD8+ T cells. Activation of CD8+ T cells by supplementation with αPD-1 antibody eliminated tumors and induced an immune memory in the cured mice. Mechanistically, an early response to trametinib treatment sensitized tumors to αPD-1-supplementation by attenuating the expression of tumor-derived CSF-1, which reduced the abundance of two CSF-1R+CD11c+ MDSC populations in the TME. In contrast, prolonged treatment with trametinib abolished the antitumor activity of αPD-1, because tumor cells undergoing the epithelial to mesenchymal transition in response to trametinib restored CSF-1 expression and recreated an immune-suppressive TME.Our findings provide the rationale for testing the trametinib/αPD-1 combination in HNC and highlight the importance of sensitizing tumors to αPD-1 by using MEK1/2 to interfere with the tumor-host interaction. Moreover, we describe the concept that treatment of cancer with a targeted therapy transiently induces an immune-active microenvironment, and supplementation of immunotherapy during this time further activates the antitumor machinery to cause tumor elimination.

Unraveling the promise and limitations of CRISPR/Cas system in natural product research: Approaches and challenges

Abstract: An incredible array of natural products is produced by plants that serve several ecological functions, including protecting them from herbivores and microbes, attracting pollinators, and dispersing seeds. In addition to their obvious medical applications, natural products serve as flavoring agents, fragrances, and many other uses by humans. With the increasing demand for natural products and the development of various gene engineering systems, researchers are trying to modify the plant genome to increase the biosynthetic pathway of the compound of interest or blocking the pathway of unwanted compound synthesis. The clustered regularly interspaced short palindromic repeats (CRISPR)/Cas9 has had widespread success in genome editing due to the system's high efficiency, ease of use, and accuracy which revolutionized the genome editing system in living organisms. This study highlights the method of the CRISPR/Cas system, its application in different organisms including microbes, algae, fungi, and also higher plants in natural product research, and its shortcomings and future prospects.

Diabetic ketoacidosis in pregnancy – Case series, pathophysiology, and review of the literature

Abstract: Diabetic ketoacidosis (DKA) during pregnancy is a life-threatening emergency for both the mother and the fetus. The pathophysiology of DKA in pregnancy has its own characteristics due to multiple factors, such as insulin resistance, accelerated starvation and respiratory alkalosis, thus creating ketosis-prone state, with DKA occurring at milder degrees of hyperglycemia, even in normoglycemic levels, which can result in delayed diagnosis and treatment with potential for adverse metabolic consequences.In this article, we presented 8 clinical cases of DKA during pregnancy. We discuss the spectrum of the clinical picture, the entity of euglycemic DKA vs hyperglycemic DKA, the period of pregnancy in appearance of episode of DKA and triggers of DKA.The treatment of DKA in pregnant women must be started immediately and must be accentuated on intravenous fluids, insulin and electrolyte replacement. DKA in pregnancy may be euglycemic. Prevention, early recognition, immediate hospitalization, and aggressive management remain the cornerstones in DKA management in pregnancy.

What Are the Oxidizing Intermediates in the Fenton and Fenton-like Reactions? A Perspective

Abstract: The Fenton and Fenton-like reactions are of major importance due to their role as a source of oxidative stress in all living systems and due to their use in advanced oxidation technologies. For many years, there has been a debate whether the reaction of FeII(H2O)62+ with H2O2 yields OH• radicals or FeIV=Oaq. It is now known that this reaction proceeds via the formation of the intermediate complex (H2O)5FeII(O2H)+/(H2O)5FeII(O2H2)2+ that decomposes to form either OH• radicals or FeIV=Oaq, depending on the pH of the medium. The intermediate complex might also directly oxidize a substrate present in the medium. In the presence of FeIIIaq, the complex FeIII(OOH)aq is formed. This complex reacts via FeII(H2O)62+ + FeIII(OOH)aq → FeIV=Oaq + FeIIIaq. In the presence of ligands, the process often observed is Ln(H2O)5-nFeII(O2H) → L•+ + Ln-1FeIIIaq. Thus, in the presence of small concentrations of HCO3- i.e., in biological systems and in advanced oxidation processes-the oxidizing radical formed is CO3•-. It is evident that, in the presence of other transition metal complexes and/or other ligands, other radicals might be formed. In complexes of the type Ln(H2O)5-nMIII/II(O2H-), the peroxide might oxidize the ligand L without oxidizing the central cation M. OH• radicals are evidently not often formed in Fenton or Fenton-like reactions.

Phage-Encoded Sigma Factors Alter Bacterial Dormancy

Abstract: By entering a reversible state of reduced metabolic activity, dormant microorganisms are able to tolerate suboptimal conditions that would otherwise reduce their fitness. Dormancy may also benefit bacteria by serving as a refuge from parasitic infections. Here, we focus on dormancy in the Bacillota, where endospore development is transcriptionally regulated by the expression of sigma factors. A disruption of this process could influence the survivorship or reproduction of phages that infect spore-forming hosts with implications for coevolutionary dynamics. We characterized the distribution of sigma factors in over 4,000 genomes of diverse phages capable of infecting hosts that span the bacterial domain. From this, we identified homologs of sporulation-specific sigma factors in phages that infect spore-forming hosts. Unlike sigma factors required for phage reproduction, we provide evidence that sporulation-like sigma factors are nonessential for lytic infection. However, when expressed in the spore-forming Bacillus subtilis, some of these phage-derived sigma factors can activate the bacterial sporulation gene network and lead to a reduction in spore yield. Our findings suggest that the acquisition of host-like transcriptional regulators may allow phages to manipulate a complex and ancient trait in one of the most abundant cell types on Earth. IMPORTANCE As obligate parasites, phages exert strong top-down pressure on host populations with eco-evolutionary implications for community dynamics and ecosystem functioning. The process of phage infection, however, is constrained by bottom-up processes that influence the energetic and nutritional status of susceptible hosts. Many phages have acquired auxiliary genes from bacteria, which can be used to exploit host metabolism with consequences for phage fitness. In this study, we demonstrate that phages infecting spore-forming bacteria carry homologs of sigma factors, which their hosts use to orchestrate gene expression during spore development. By tapping into regulatory gene networks, phages may manipulate the physiology and survival strategies of nongrowing bacteria in ways that influence host-parasite coevolution.