Miracle-dz/UniFAR-FTUs huggingface dataset:
Behavior of Eosinophil Counts in Recovered and Deceased COVID-19 Patients over the Course of the Disease

Knowledge about the immune responses against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection, particularly regarding the function of eosinophils, has been steadily emerging recently. There exists controversy regarding the implications of eosinophils in the coronavirus disease 2019 (COVID-19)’s pathology. We report a retrospective cohort study including the comparison of leukocyte counts in COVID-19 patients, considering the outcomes of recovery (n = 59) and death (n = 60). Among the different types of leukocytes, the eosinophil counts were those that showed the greatest difference between recovered and deceased patients. Eosinopenia (eosinophil count < 0.01 × 109/L) was more frequently observed in deceased than recovered patients (p = 0.0012). The eosinophil counts more rapidly increased and showed a greater proportion over the course of the disease in the recovered than deceased patients. Furthermore, the estimated survival rate was greater in patients without eosinopenia than in patients with eosinopenia (p = 0.0070) during hospitalization. Importantly, recovered but not deceased patients showed high negative correlations of the eosinophils with the neutrophil-to-lymphocyte ratio (NLR) and neutrophil counts at Day 9 of the onset of clinical symptoms (p ≤ 0.0220). Our analysis suggests that eosinopenia may be associated with unfavorable disease outcomes and that the eosinophils have a beneficial function in COVID-19 patients, probably contributing by controlling the exacerbated inflammation induced by neutrophils.
Therapeutic Potential of IL-15 and N-803 in HIV/SIV Infection

IL-15, a proinflammatory cytokine critical for the generation, maintenance, and homeostasis of T cell responses, is produced naturally in response to HIV/SIV infection, but has also demonstrated therapeutic potential. IL-15 can boost CD4+ and CD8+ T cell and NK cell proliferation, activation, and function. However, IL-15 treatment may cause aberrant immune activation and accelerated disease progression in certain circumstances. Moreover, the relationship between the timing of IL-15 administration and disease progression remains unclear. The IL-15 superagonist N-803 was developed to expand the therapeutic potential of IL-15 by maximizing its tissue distribution and half-life. N-803 has garnered enthusiasm recently as a way to enhance the innate and cellular immune responses to HIV/SIV by improving CD8+ T cell recognition and killing of virus-infected cells and directing immune cells to mucosal sites and lymph nodes, the primary sites of virus replication. N-803 has also been evaluated in “shock and kill” strategies due to its potential to reverse latency (shock) and enhance antiviral immunity (kill). This review examines the current literature about the effects of IL-15 and N-803 on innate and cellular immunity, viral burden, and latency reversal in the context of HIV/SIV, and their therapeutic potential both alone and combined with additional interventions such as antiretroviral therapy (ART) and vaccination.
Characterizing Surgical and Radiotherapy Outcomes in Non-metastatic High-Risk Prostate Cancer: A Systematic Review and Meta-Analysis

Background Identifying the optimal management of high-risk non-metastatic prostate cancer (PCa) is an important public health concern, given the large burden of this disease. We performed a meta-analysis of studies comparing PCa-specific mortality (CSM) among men diagnosed with high-risk non-metastatic PCa who were treated with primary radiotherapy (RT) and radical prostatectomy (RP). Methods Medline and Embase were searched for articles between January 1, 2005, and February 11, 2020. After title and abstract screening, two authors independently reviewed full-text articles for inclusion. Data were abstracted, and a modified version of the Newcastle-Ottawa Scale, involving a comprehensive list of confounding variables, was used to assess the risk of bias. Results Fifteen studies involving 131,392 patients were included. No difference in adjusted CSM in RT relative to RP was shown (hazard ratio, 1.02 [95% confidence interval: 0.84, 1.25]). Increased CSM was found in a subgroup analysis comparing external beam radiation therapy (EBRT) with RP (1.35 [1.10, 1.68]), whereas EBRT combined with brachytherapy (BT) versus RP showed lower CSM (0.68 [0.48, 0.95]). All studies demonstrated a high risk of bias as none fully adjusted for all confounding variables. Conclusion We found no difference in CSM between men diagnosed with non-metastatic high-risk PCa and treated with RP or RT; however, this is likely explained by increased CSM in men treated with EBRT and decreased CSM in men treated with EBRT + BT studies relative to RP. High risk of bias in all studies identifies the need for better data collection and confounding control in the PCa research.
Chimeric VLPs Bearing VP60 from Two Serotypes of Rabbit Haemorrhagic Disease Virus Are Protective against Both Viruses

The VP60 capsid protein from rabbit haemorrhagic disease virus (RHDV), the causative agent of one of the most economically important disease in rabbits worldwide, forms virus-like particles (VLPs) when expressed using heterologous protein expression systems such as recombinant baculovirus, yeasts, plants or mammalian cell cultures. To prevent RHDV dissemination, it would be beneficial to develop a bivalent vaccine including both RHDV GI.1- and RHDV GI.2-derived VLPs to achieve robust immunisation against both serotypes. In the present work, we developed a strategy of production of a dual-serving RHDV vaccine co-expressing the VP60 proteins from the two RHDV predominant serotypes using CrisBio technology, which uses Tricholusia ni insect pupae as natural bioreactors, which are programmed by recombinant baculovirus vectors. Co-infecting the insect pupae with two baculovirus vectors expressing the RHDV GI.1- and RHDV GI.2-derived VP60 proteins, we obtained chimeric VLPs incorporating both proteins as determined by using serotype-specific monoclonal antibodies. The resulting VLPs showed the typical size and shape of this calicivirus as determined by electron microscopy. Rabbits immunised with the chimeric VLPs were fully protected against a lethal challenge infection with the two RHDV serotypes. This study demonstrates that it is possible to generate a dual cost-effective vaccine against this virus using a single production and purification process, greatly simplifying vaccine manufacturing.
Wastewater Valorization: Practice around the World at Pilot- and Full-Scale

Over the last few years, wastewater treatment plants (WWTPs) have been rebranded as water resource recovery facilities (WRRFs), which recognize the resource recovery potential that exists in wastewater streams. WRRFs contribute to a circular economy by not only producing clean water but by recovering valuable resources such as nutrients, energy, and other bio-based materials. To this aim, huge efforts in technological progress have been made to valorize sewage and sewage sludge, transforming them into valuable resources. This review summarizes some of the widely used and effective strategies applied at pilot- and full-scale settings in order to valorize the wastewater treatment process. An overview of the different technologies applied in the water and sludge line is presented, covering a broad range of resources, i.e., water, biomass, energy, nutrients, volatile fatty acids (VFA), polyhydroxyalkanoates (PHA), and exopolymeric substances (EPS). Moreover, guidelines and regulations around the world related to water reuse and resource valorization are reviewed.
Mechanical Behavior of Blood Vessels: Elastic and Viscoelastic Contributions

Simple Summary A frequent type of injuries in traffic collisions and falls from a moderate height is associated with subdural hematomas caused by the mechanical failure of cerebral bridging veins, which link the superior sagittal sinus to the brain. For this reason, both to design safe restraint systems for motor vehicles and to study how these injuries occur, it is important to study the mechanical properties of the bridging veins. Although the mechanical properties of bridging veins have been studied for the last half century, some viscoelastic effects in these vessels that alter their mechanical response have not been analyzed in detail until now. This is the first study that measures, quantifies, and models these viscoelastic effects, thus improving our knowledge of the mechanical response of cerebral bridging veins. Abstract The mechanical properties of the cerebral bridging veins (CBVs) were studied using advanced microtensile equipment. Detailed high-quality curves were obtained at different strain rates, showing a clearly nonlinear stress–strain response. In addition, the tissue of the CBVs exhibits stress relaxation and a preconditioning effect under cyclic loading, unequivocal indications of viscoelastic behavior. Interestingly, most previous literature that conducts uniaxial tensile tests had not found significant viscoelastic effects in CBVs, but the use of more sensitive tests allowed to observe the viscoelastic effects. For that reason, a careful mathematical analysis is presented, clarifying why in uniaxial tests with moderate strain rates, it is difficult to observe any viscoelastic effect. The analysis provides a theoretical explanation as to why many recent studies that investigated mechanical properties did not find a significant viscoelastic effect, even though in other circumstances, the CBV tissue would clearly exhibit viscoelastic behavior. Finally, this study provides reference values for the usual mechanical properties, as well as calculations of constitutive parameters for nonlinear elastic and viscoelastic models that would allow more accurate numerical simulation of CBVs in Finite Element-based computational models in future works.
3D-Printable Nanocellulose-Based Functional Materials: Fundamentals and Applications

Nanomaterials obtained from sustainable and natural sources have seen tremendous growth in recent times due to increasing interest in utilizing readily and widely available resources. Nanocellulose materials extracted from renewable biomasses hold great promise for increasing the sustainability of conventional materials in various applications owing to their biocompatibility, mechanical properties, ease of functionalization, and high abundance. Nanocellulose can be used to reinforce mechanical strength, impart antimicrobial activity, provide lighter, biodegradable, and more robust materials for packaging, and produce photochromic and electrochromic devices. While the fabrication and properties of nanocellulose are generally well established, their implementation in novel products and applications requires surface modification, assembly, and manufacturability to enable rapid tooling and scalable production. Additive manufacturing techniques such as 3D printing can improve functionality and enhance the ability to customize products while reducing fabrication time and wastage of materials. This review article provides an overview of nanocellulose as a sustainable material, covering the different properties, preparation methods, printability and strategies to functionalize nanocellulose into 3D-printed constructs. The applications of 3D-printed nanocellulose composites in food, environmental, and energy devices are outlined, and an overview of challenges and opportunities is provided.
Mutation Rates, Mutation Frequencies, and Proofreading-Repair Activities in RNA Virus Genetics

The error rate displayed during template copying to produce viral RNA progeny is a biologically relevant parameter of the replication complexes of viruses. It has consequences for virus–host interactions, and it represents the first step in the diversification of viruses in nature. Measurements during infections and with purified viral polymerases indicate that mutation rates for RNA viruses are in the range of 10−3 to 10−6 copying errors per nucleotide incorporated into the nascent RNA product. Although viruses are thought to exploit high error rates for adaptation to changing environments, some of them possess misincorporation correcting activities. One of them is a proofreading-repair 3′ to 5′ exonuclease present in coronaviruses that may decrease the error rate during replication. Here we review experimental evidence and models of information maintenance that explain why elevated mutation rates have been preserved during the evolution of RNA (and some DNA) viruses. The models also offer an interpretation of why error correction mechanisms have evolved to maintain the stability of genetic information carried out by large viral RNA genomes such as the coronaviruses.
Has the Phase of the Menstrual Cycle Been Considered in Studies Investigating Pressure Pain Sensitivity in Migraine and Tension-Type Headache: A Scoping Review

Objective: The aim of this scoping review was to identify if the phase of the menstrual cycle was considered in observational studies comparing pressure pain sensitivity between women with migraine or tension-type headache (TTH) and headache-free women. Methods: A systematic electronic literature search in PubMed, Medline, Web of Science, Scopus, and CINAHL databases was conducted. Observational studies including one or more groups with TTH and/or migraine comparing pressure pain thresholds (PPTs) were included. The methodological quality (risk of bias) was assessed with the Newcastle-Ottawa Scale. Authors, objectives, inclusion/exclusion criteria, size sample, female sample, tool to assess PPTs, mean age, and the use of any medication were extracted and analyzed independently by two authors. Results: From a total of 1404 and 1832 identified articles for TTH and migraine, 30 and 18 studies satisfied the criteria and were included. Nineteen (63.4%) studies assessing TTH patients and eleven (61.1%) assessing migraine patients showed a high risk of bias. The most common flaws were attributed to improper selection of control and control over other additional factors. Based on the systematic review, just one study including TTH and one including migraine patients considered the menstrual cycle. Conclusion: The results of this scoping review identified that the phase of the menstrual cycle has been rarely considered in studies investigating sensitivity to pressure pain in primary headaches, such as TTH or migraine, although there is evidence showing the relevance of the phase of the menstrual cycle in pain perception.
Structural Analysis of the Menangle Virus P Protein Reveals a Soft Boundary between Ordered and Disordered Regions

The paramyxoviral phosphoprotein (P protein) is the non-catalytic subunit of the viral RNA polymerase, and coordinates many of the molecular interactions required for RNA synthesis. All paramyxoviral P proteins oligomerize via a centrally located coiled-coil that is connected to a downstream binding domain by a dynamic linker. The C-terminal region of the P protein coordinates interactions between the catalytic subunit of the polymerase, and the viral nucleocapsid housing the genomic RNA. The inherent flexibility of the linker is believed to facilitate polymerase translocation. Here we report biophysical and structural characterization of the C-terminal region of the P protein from Menangle virus (MenV), a bat-borne paramyxovirus with zoonotic potential. The MenV P protein is tetrameric but can dissociate into dimers at sub-micromolar protein concentrations. The linker is globally disordered and can be modeled effectively as a worm-like chain. However, NMR analysis suggests very weak local preferences for alpha-helical and extended beta conformation exist within the linker. At the interface between the disordered linker and the structured C-terminal binding domain, a gradual disorder-to-order transition occurs, with X-ray crystallographic analysis revealing a dynamic interfacial structure that wraps the surface of the binding domain.
Inulin-Based Polymeric Micelles Functionalized with Ocular Permeation Enhancers: Improvement of Dexamethasone Permeation/Penetration through Bovine Corneas

Ophthalmic drug delivery is still a challenge due to the protective barriers of the eye. A common strategy to promote drug absorption is the use of ocular permeation enhancers, while an innovative approach is the use of polymeric micelles. In the present work, the two mentioned approaches were coupled by conjugating ocular permeation enhancers (PEG2000, carnitine, creatine, taurine) to an inulin-based co-polymer (INU-EDA-RA) in order to obtain self-assembling biopolymers with permeation enhancer properties for the hydrophobic drug dexamethasone (DEX). Inulin derivatives were properly synthetized, were found to expose about 2% mol/mol of enhancer molecules in the side chain, and resulted able to self-assemble at various concentrations by varying the pH and the ionic strength of the medium. Moreover, the ability of polymeric micelles to load dexamethasone was demonstrated, and size, mucoadhesiveness, and cytocompatibility against HCE cells were evaluated. Furthermore, the efficacy of the permeation enhancer was evaluated by ex vivo permeation studies to determine the performance of the used enhancers, which resulted in PEG2000 > CAR > TAU > CRE, while entrapment ability studies resulted in CAR > TAU > PEG2000 > CRE, both for fluorescent-labelled and DEX-loaded micelles. Finally, an increase in terms of calculated Kp and Ac parameters was demonstrated, compared with the values calculated for DEX suspension.
Endothelium-Derived Hyperpolarizing Factor (EDHF) Mediates Acetylsalicylic Acid (Aspirin) Vasodilation of Pregnant Rat Mesenteric Arteries

Acetylsalicylic acid (aspirin) exhibits a broad range of activities, including analgesic, antipyretic, and antiplatelet properties. Recent clinical studies also recommend aspirin prophylaxis in women with a high risk of pre-eclampsia, a major complication of pregnancy characterized by hypertension. We investigated the effect of aspirin on mesenteric resistance arteries and found outdiscovered the molecular mechanism underlying this action. Aspirin (10−12–10−6 M) was tested on pregnant rat mesenteric resistance arteries by a pressurized arteriography. Aspirin was investigated in the presence of several inhibitors of: (a) nitric oxide synthase (L-NAME 2 × 10−4 M); (b) cyclooxygenase (Indomethacin, 10−5 M); (c) Ca2+-activated K+ channels (Kca): small conductance (SKca, Apamin, 10−7 M), intermediate conductance (IKca, TRAM34, 10−5 M), and big conductance (BKca, paxilline, 10−5 M); and (d) endothelial-derived hyperpolarizing factor (high KCl, 80 mM). Aspirin caused a concentration-dependent vasodilation. Aspirin-vasodilation was abolished by removal of endothelium or by high KCl. Furthermore, preincubation with either apamin plus TRAM-34 or paxillin significantly attenuated aspirin vasodilation (p < 0.05). For the first time, we showed that aspirin induced endothelium-dependent vasodilation in mesenteric resistance arteries through the endothelial-derived hyperpolarizing factor (EDHF) and calcium-activated potassium channels. By activating this molecular mechanism, aspirin may lower peripheral vascular resistance and be beneficial in pregnancies complicated by hypertension.
Insights into the Genetic Evolution of Duck Hepatitis A Virus in Egypt

Simple Summary The accumulation of point mutations and/or recombination between different serotypes drives the evolution of the duck hepatitis A viruses (DHAVs). Duck viral hepatitis, caused by DHAV, is a highly infectious disease that has been detected in Egypt since 1970. Low performance, nervous signs and sudden deaths of young ducklings were the main characteristics of the disease. The aim of this study was to identify the causative agent through viral and molecular detection for the causative virus. The causative virus was isolated in embryonated duck eggs (EDEs), with complete genome sequencing that indicate the clustering of our isolates reported in this study with Chinese duck hepatitis virus 1 that may help in new vaccine manufacturing and the development of a more sensitive diagnostic assays. Future studies to evaluate the potential protection of available commercial vaccines against the newly detected isolates will be needed. Abstract Duck hepatitis virus (DHV) is one of the commercially important diseases of ducklings worldwide. It is an acute and highly infectious disease of ducklings caused by three different serotypes (1–3) of duck hepatitis A virus (DHAV), and serotype 1 is the most common in poultry. To date, little is known about the prevalence and genetic characterisation of DHAV-1 in Egypt. In the current study, isolation and complete genomic analyses of DHAVs circulating in commercial duck farms in different Egyptian governorates were conducted. A total of eighteen samples were collected from six Egyptian governorates of 3–11 days old ducklings (Pekin and Mullard) with a history of nervous signs and high mortality rates. Five out of eighteen (5/18) samples were screened positive for the DHAV-1 based on the VP1 gene. These samples were individually used for virus isolation in embryonated duck embryos (EDE), followed by complete genome sequencing. Phylogenomic analyses showed that DHAV serotype I; genotype I were diversified into four different groups (1–4). Most of the recent circulating Egyptian DHAV strains are clustered within group 4, while isolates characterised within this study were clustered within group 1. Recombination analyses revealed that the emergence of a new recombinant virus—DHAV-1 strain Egypt-10/2019—through recombination. Likewise, the selective pressure analyses showed the existence, inside or near areas of the viral attachment or related functions, of positive scores highlighting the importance of natural selection and viral evolution mechanism at different protein domains. The findings of this study provide updated information on the epidemiological and genetic features of DHAV-1 strains and underscore the importance of DHAV surveillance as well as re-evaluation for currently used vaccines.
Associations between Psychosocial Working Conditions and Quality of Care (i.e., Slips and Lapses, and Perceived Social Interactions with Patients)—A Cross-Sectional Study among Medical Assistants

Adverse psychosocial working conditions in the health care sector are widespread and have been associated with a reduced quality of patient care. Medical assistants (MA) assume that their unfavorable working conditions predominantly lead to a poorer quality of care in terms of slips and lapses, and poorer social interactions with patients. We examined those associations for the first time among MAs. A total of 944 MAs in Germany participated in a survey (September 2016–April 2017). Psychosocial working conditions were measured by the effort-reward imbalance (ERI) questionnaire and a questionnaire specifically designed for MAs. Slips and lapses (3 items, e.g., measurement or documentation errors) and the quality of interactions (3 items) with patients were measured by a questionnaire developed by the study team based on prior qualitative research. We ran Poisson regression to estimate multivariable prevalence ratios (PRs). The ERI ratio and MA-specific working conditions were significantly associated with frequent self-reported slips and lapses (PR = 2.53 and PR ≥ 1.22, respectively) or poor interactions with patients (PR = 3.62 and PR ≥ 1.38, respectively) due to work stress. Our study suggests that various types of adverse psychosocial working conditions are associated with perceptions of slips and lapses or poorer interaction with patients due to work stress among MAs.