bluuebunny/crossref_metadata_2025 huggingface dataset:
The Phospholipase Activity of Ammodytoxin, a Prototype Snake Venom β-Neurotoxin, Is Not Obligatory for Cell Internalisation and Translocation to Mitochondria
Authors: Ivanušec Adrijan , Šribar Jernej , Veranič Peter , Križaj Igor
Published: May 2022

β-Neurotoxins are secreted phospholipase A2 molecules that inhibit transmission in neuromuscular synapses by poisoning the motor neurons. These toxins specifically and rapidly internalise into the nerve endings of motor neurons. Ammodytoxin (Atx) is a prototype β-neurotoxin from the venom of the nose-horned viper (Vipera ammodytes ammodytes). Here, we studied the relevance of the enzymatic activity of Atx in cell internalisation and subsequent intracellular movement using transmission electron microscopy (TEM). We prepared a recombinant, enzymatically inactive mutant of Atx, Atx(D49S), labelled with gold nanoparticles (GNP), and incubated this with PC12 cells, to analyse its localisation by TEM. Atx(D49S)-GNP internalised into the cells. Inside the cells, Atx(D49S)-GNP was detected in different vesicle-like structures, cytosol, endoplasmic reticulum and mitochondria, where it was spotted in the intermembrane space and matrix. Co-localization of fluorescently labelled Atx(D49S) with mitochondria in PC12 cells by confocal fluorescence microscopy confirmed the reliability of results generated using Atx(D49S)-GNP and TEM and allowed us to conclude that the phospholipase activity of Atx is not obligatory for its cell internalisation and translocation into the mitochondrial intermembrane space and matrix.
Decrease in Aflatoxin M1 Concentration in Milk during Cholesterol Removal by Application of β-Cyclodextrin
Authors: Šimko Peter , Kolarič Lukáš
Published: May 2022

Approximately one-third of humankind is chronically exposed to the carcinogenic aflatoxin M1 contained in milk. As β-cyclodextrin is frequently used in the food industry, its effect on aflatoxin M1 concentration was investigated during cholesterol removal from milk due to the similarity among the physicochemical properties of aflatoxin M1 and cholesterol. Moreover, the elimination of cholesterol using β-cyclodextrin has been successfully applied in many studies without any substantial effect on the quality of the treated milk. Therefore, milk samples were spiked with aflatoxin M1 within the range from 0.20 to 2.00 µg/kg, and cholesterol removal was carried out by 2.0% (w/w) β-cyclodextrin addition, as this concentration is enough for the sufficient removal of cholesterol. It was found that the mean cholesterol concentration decreased by 92.3%, while the aflatoxin M1 concentration decreased to 0.53 ± 0.04 µg/kg, i.e., by 39.1% after treatment (n = 2). This mitigation procedure itself is easy and inexpensive and thus is fully applicable with a high potential for complete decontamination of aflatoxin M1 milk. This method will therefore considerably improve the food safety issues associated with aflatoxin M1 presence in milk and dairy products.
Treatment of Depression with Botulinum Toxin
Authors: Wollmer Marc Axel , Magid Michelle , Kruger Tillmann H. C. , Finzi Eric
Published: May 2022

Injection of botulinum toxin (BoNT) into the glabellar region of the face is a novel therapeutic approach in the treatment of depression. This treatment method has several advantages, including few side effects and a long-lasting, depot-like effect. Here we review the clinical and experimental evidence for the antidepressant effect of BoNT injections as well as the theoretical background and possible mechanisms of action. Moreover, we provide practical instructions for the safe and effective application of BoNT in the treatment of depression. Finally, we describe the current status of the clinical development of BoNT as an antidepressant and give an outlook on its potential future role in the management of mental disorders.
Avoiding Allostatic Load: Black Male Collegians and the Quest for Well-Being
Authors: Livingston Val , Jackson-Nevels Breshell , Dinnerson Quincy L.
Published: May 2022

The literature suggests that African American/Black males are less likely to seek professional assistance for mental health and other personal concerns than African American/Black females and that they are more likely to seek informal help for mental health problems than professional help. Are there circumstances where African American/Black males would seek professional help over informal help? This research updates what is currently known about African American/Black male collegians’ help-seeking behaviors and the circumstances or conditions that might influence professional help-seeking. Secondary data illustrating the help-seeking behaviors of African American/Black male collegians at an urban HBCU was examined to identify patterns or trends during the first semester of 2018 and 2019. De-identified data sheets for 103 African American/Black males were examined to identify referral sources, current mental health concerns, and past mental health concerns. African American/Black male and female collegians sought professional assistance for similar concerns: family problems, couples problems, peer interpersonal problems, depression, anxiety, and stress. Black males were more likely to self-refer for professional assistance than seek informal assistance. Implications for university counseling centers are explored.
Prospects for Probing Axionlike Particles at a Future Hadron Collider through Top Quark Production
Authors: Hosseini Yasaman , Mohammadi Najafabadi Mojtaba
Published: May 2022

Axionlike particles (ALPs) emerge from spontaneously broken global symmetries in high energy extensions of the Standard Model (SM). This causes ALPs to be among the objectives of future experiments that intend to search for new physics beyond the SM. We discuss the reach of future pp collider FCC-hh in probing the ALP model parameters through top quark pair production associated with ALP (tt¯+ALP) in a model-independent approach. The search is performed in the semi-leptonic decay mode of tt¯ and the analysis is performed using a parametric simulation of the detector response for a projected integrated luminosity of 30ab−1. It is shown that tt¯+ALP production at the FCC-hh is a promising channel with significant sensitivity to probe the ALP coupling with gluons. The ALP coupling with gluons obtained from HL-LHC and other experiments is presented for comparison.
Infrared Spectral Energy Distribution and Variability of Active Galactic Nuclei: Clues to the Structure of Circumnuclear Material
Authors: Lyu Jianwei , Rieke George
Published: May 2022

The active galactic nucleus (AGN) phenomenon results from a supermassive black hole accreting its surrounding gaseous and dusty material. The infrared (IR) regime provides most of the information to characterize the dusty structures that bridge from the galaxy to the black hole, providing clues to the black hole growth and host galaxy evolution. Over the past several decades, with the commissioning of various ground, airborne and space IR observing facilities, our interpretations of the AGN circumnuclear structures have advanced significantly through an improved understanding of how their dust emission changes as a function of wavelength and how the heating of the dusty structures responds to variations in the energy released from the central engine. In this review, we summarize the current observational knowledge of the AGN IR broad-band spectral energy distributions (SEDs) and the IR time variability behavior covering large ranges of AGN luminosity and redshift, and discuss some first-order insights into the obscuring structures and host galaxy IR properties that can be obtained by integrating the relevant observations into a coherent picture.
The Higgs Mechanism and Cosmological Constant Today
Authors: Dymnikova Irina
Published: May 2022

The Higgs mechanism, as responsible for the first inflation, powers the initial accelerated expansion and further preheating via the symmetry breaking from its false vacuum state corresponding to the Sitter vacuum of the GUT scale with Λ=8πGρΛ, whose decay provides necessary energetic support. Here we address the question of the possibility of symmetry restoration of the Higgs field at the presently observed vacuum scale which would make it responsible for the today value of the cosmological constant λ=8πGρλ. We find the existence of the possibility of symmetry restoration in the minisuperspace model of quantum cosmology and show that λ today must have a non-zero value.
Interpretation of the Spectra and Anisotropy of Galactic Cosmic Rays
Authors: Li Aifeng , Yin Shiyu , Liu Maoyuan , Wang Hao , Li Xiaoyu , Li Yaping
Published: May 2022

Recent measurements of the spectra and anisotropy of cosmic rays (CRs) show a fine structure that reflects the spectral hardenings of CRs nuclei at the rigidity R ∼ 200 GV followed by softenings at R ∼ 10 TV, and reveal complicated energy dependence of the amplitude and phase of anisotropy from 100 GeV to PeV. Numerous studies have shown that the existence of nearby CR sources and a local interstellar magnetic field (LIMF) near the solar system are crucial for such CR spectral and anisotropic patterns. In this work, we analyze the CR spectra of different CR components and the anisotropy considering the nearby Geminga supernova remnants (SNRs) source. In the calculation process, we also introduce the anisotropic diffusion of CRs induced by the LIMF based on the spatial-dependent propagation (SDP) model. As a result, our model can simultaneously account for the CR spectra and the anisotropy from 100 GeV to PeV. Future high-precision measurements of the CR anisotropy, for example, by the LHAASO experiment, would be of the essence in the assessment of our proposed model.
GRB Prompt Emission: Observed Correlations and Their Interpretations
Authors: Parsotan Tyler , Ito Hirotaka
Published: May 2022

The prompt emission of Gamma Ray Bursts (GRBs) is still an outstanding question in the study of these cataclysmic events. Part of what makes GRBs difficult to study is how unique each event seems to be. However, aggregating many GRB observations and analyzing the population allows us to obtain a better understanding of the emission mechanism that produces the observed prompt emission. In this review, we outline some of the most prevalent correlations that have emerged from GRB prompt emission observations and how these correlations are interpreted in relation to physical properties and prompt emission models of GRB.
Urban Climate Justice, Human Health, and Citizen Science in Nairobi’s Informal Settlements
Authors: Corburn Jason , Njoroge Patrick , Weru Jane , Musya Maureen
Published: May 2022

Urban informal settlements or slums are among the most vulnerable places to climate-change-related health risks. Yet, little data exist documenting environmental and human health vulnerabilities in slums or how to move research to action. Citizen science, where residents co-define research objectives with professionals, collect and analyze data, and help translate findings into ameliorative actions, can help fill data gaps and contribute to more locally relevant climate justice interventions. This paper highlights a citizen-science, climate justice planning process in the Mukuru informal settlement of Nairobi, Kenya. We describe how residents, non-governmental organizations and academics partnered to co-create data-gathering processes and generated evidence to inform an integrated, climate justice strategy called the Mukuru Special Planning Area, Integrated Development Plan. The citizen science processes revealed that <1% of residents had access to a private in-home toilet, and 37% lacked regular access to safe and affordable drinking water. We found that 42% of households were subject to regular flooding, 39% reported fair or poor health, and 40% reported a child in the household was stunted. These and other data were used in a community planning process where thousands of residents co-designed improvement and climate change adaptation strategies, such as flood mitigation, formalizing roads and pathways with drainage, and a water and sanitation infrastructure plan for all. We describe the participatory processes used by citizen scientists to generate data and move evidence into immediate actions to protect human health and a draft a long-range, climate justice strategy. The processes used to create the Mukuru Special Planning Area redevelopment plan suggest that participatory, citizen-led urban science can inform local efforts for health equity and global goals of climate justice.
The Process of Filopodia Induction during HPV Infection
Authors: Biondo Alyssa , Meneses Patricio I.
Published: May 2022

Human Papillomavirus 16 (HPV16) infects mucosal and epithelial cells and has been identified as a high-risk HPV type that is an etiologic agent of human cancers. The initial infectious process, i.e., the binding of the virus particle and its entry into the host cell, has been studied extensively, although it is not fully understood. There is still a gap in understanding the steps by which the virus is able to cross the plasma membrane after receptor binding. In this study, we demonstrate that after HPV16 comes into contact with a plasma membrane receptor, there are cytoskeletal changes resulting in an increase of filopodia numbers. This increase in filopodia numbers was transient and was maintained during the first two hours after virus addition. Our data show that there is a statistically significant increase in infection when filopodia numbers are increased by the addition of drug and virus simultaneously, and a decrease in virus infection when filopodia formation is inhibited. We describe that HPV16 binding results in the activation of Cdc42 GTPase that in turn results in an increase in filopodia. siRNA directed at Cdc42 GTPase resulted in a statistically significant reduction of infection and a corresponding lack of filopodia induction.
Burden and Trends of Acute Viral Hepatitis in Asia from 1990 to 2019
Authors: Liu Qiao , Liu Min , Liu Jue
Published: May 2022

Asia has a very high burden of acute hepatitis; thus, a comprehensive study of the current burden and long-term trends of acute hepatitis in Asia is needed. We aimed to assess the current status and trends from 1990 to 2019 of acute hepatitis burden in Asia, using the data from the Global Burden of Diseases Study 2019 (GBD 2019) results. Methods: We used the data from the GBD 2019. Absolute death, incidence, and disability adjusted life years (DALY) number and rate of acute hepatitis in Asia were derived from the database from 1990 to 2019. Age-standardized mortality, incidence and DALY rates (ASMR, ASIR and ASDR) were used to compare populations in different regions and times. The estimated annual percentage change (EAPC) in the rates quantified the trends of the acute hepatitis burden. Results: From 1990 to 2019, the ASMR and ASDR of acute hepatitis decreased significantly at different paces, with the largest decrease in acute hepatitis C and the smallest in acute hepatitis E. The ASIR of acute hepatitis decreased relatively slowly, by an average of 0.06% (95% CI, 0.05–0.08%) per year in acute hepatitis A, 0.91% (0.64–1.18%) per year in acute hepatitis C and 0.26% (0.24–0.28%) per year in acute hepatitis E; while the ASIR of acute hepatitis B decreased by an average of 1.95% (1.08–2.11) per year. From 1990 to 2019, the incidence rate of acute hepatitis A increased in most age groups (from the age of 5 to 70), with the 50–55 years group having the fastest increase by an average of 1.81% (95% CI, 1.67–1.95%) per year. In 2019, Afghanistan had the highest ASMR (10.44 per 100,000) and ASDR (357.85 per 100,000) of acute hepatitis, and the highest ASIR was in Mongolia (4703.14 per 100,000). Conclusions: In Asia, the burden of acute viral hepatitis was at a relatively high level, compared with the other four continents. International cooperation and multifaceted and multisectoral actions are needed for Asian countries to eliminate viral hepatitis and to contribute to the global elimination of viral hepatitis.
Carriers of ADAMTS13 Rare Variants Are at High Risk of Life-Threatening COVID-19
Authors: Zguro Kristina , Baldassarri Margherita , Fava Francesca , Beligni Giada , Daga Sergio , Leoncini Roberto , Galasso Lucrezia , Cirianni Michele , Rusconi Stefano , Siano Matteo , Francisci Daniela , Schiaroli Elisabetta , Luchi Sauro , Morelli Giovanna , Martinelli Enrico , Girardis Massimo , Busani Stefano , Parisi Saverio Giuseppe , Panese Sandro , Piscopo Carmelo , Capasso Mario , Tacconi Danilo , Spertilli Raffaelli Chiara , Giliberti Annarita , Gori Giulia , Katsikis Peter D. , Lorubbio Maria , Calzoni Paola , Ognibene Agostino , Bocchia Monica , Tozzi Monica , Bucalossi Alessandro , Marotta Giuseppe , Furini Simone ,   GEN-COVID Multicenter Study, Renieri Alessandra , Fallerini Chiara
Published: May 2022

Thrombosis of small and large vessels is reported as a key player in COVID-19 severity. However, host genetic determinants of this susceptibility are still unclear. Congenital Thrombotic Thrombocytopenic Purpura is a severe autosomal recessive disorder characterized by uncleaved ultra-large vWF and thrombotic microangiopathy, frequently triggered by infections. Carriers are reported to be asymptomatic. Exome analysis of about 3000 SARS-CoV-2 infected subjects of different severities, belonging to the GEN-COVID cohort, revealed the specific role of vWF cleaving enzyme ADAMTS13 (A disintegrin-like and metalloprotease with thrombospondin type 1 motif, 13). We report here that ultra-rare variants in a heterozygous state lead to a rare form of COVID-19 characterized by hyper-inflammation signs, which segregates in families as an autosomal dominant disorder conditioned by SARS-CoV-2 infection, sex, and age. This has clinical relevance due to the availability of drugs such as Caplacizumab, which inhibits vWF–platelet interaction, and Crizanlizumab, which, by inhibiting P-selectin binding to its ligands, prevents leukocyte recruitment and platelet aggregation at the site of vascular damage.
Kinetics in HBsAg after Stopping Entecavir or Tenofovir in Patients with Virological Relapse but Not Clinical Relapse
Authors: Tseng Tzu-Ning , Kuo Yuan-Hung , Hu Tsung-Hui , Hung Chao-Hung , Wang Jing-Houng , Lu Sheng-Nan , Chen Chien-Hung
Published: May 2022

This study investigated the kinetics in HBsAg and the HBsAg loss rate after entecavir or tenofovir disoproxil fumarate (TDF) cessation in patients with chronic hepatitis B (CHB) who achieved virological suppression after virological relapse without clinical relapse. A total 504 HBeAg-negative, non-cirrhotic patients who previously received entecavir or TDF with post-treatment and who were followed up for at least 30 months were included. Of the 504 patients, 128 achieved sustained virological suppression (Group I), and 81 experienced virological relapse without clinical relapse. Of the 81 patients, 52 had intermittent or persistent HBV DNA > 2000 IU/mL (Group II), and 29 achieved persistent virological suppression (HBV DNA < 2000 IU/mL) for at least 1.5 years (Group III) after virological relapse. A generalized estimating equations analysis showed that Groups I and III experienced larger off-treatment HBsAg declines than Group II (both, p < 0.001). The post-treatment HBsAg declines of Group I and Group III were similar (p = 0.414). A multivariate analysis showed that there were no differences in the HBsAg change and HBsAg decline (p = 0.920 and 0.886, respectively) or HBsAg loss rate (p = 0.192) between Group I and Group III. The patients who achieved persistent viral suppression after HBV relapse without clinical relapse have a similar decline in HBsAg and the HBsAg loss rate as the sustained responders.
Seroprevalence and Risk Factors for Equine West Nile Virus Infections in Eastern Germany, 2020
Authors: Ganzenberg Stefanie , Sieg Michael , Ziegler Ute , Pfeffer Martin , Vahlenkamp Thomas W. , Hörügel Uwe , Groschup Martin H. , Lohmann Katharina L.
Published: May 2022

West Nile virus (WNV) infections were first detected in Germany in 2018, but information about WNV seroprevalence in horses is limited. The study’s overall goal was to gather information that would help veterinarians, horse owners, and veterinary-, and public health- authorities understand the spread of WNV in Germany and direct protective measures. For this purpose, WNV seroprevalence was determined in counties with and without previously registered WNV infections in horses, and risk factors for seropositivity were estimated. The cohort consisted of privately owned horses from nine counties in Eastern Germany. A total of 940 serum samples was tested by competitive panflavivirus ELISA (cELISA), and reactive samples were further tested by WNV IgM capture ELISA and confirmed by virus neutralization test (VNT). Information about potential risk factors was recorded by questionnaire and analyzed by logistic regression. A total of 106 serum samples showed antibodies against flaviviruses by cELISA, of which six tested positive for WNV IgM. The VNT verified a WNV infection for 54 samples (50.9%), while 35 sera neutralized tick-borne encephalitis virus (33.0%), and eight sera neutralized Usutu virus (7.5%). Hence, seroprevalence for WNV infection was 5.8% on average and was significantly higher in counties with previously registered infections (p = 0.005). The risk factor analysis showed breed type (pony), housing in counties with previously registered infections, housing type (24 h turn-out), and presence of outdoor shelter as the main significant risk factors for seropositivity. In conclusion, we estimated the extent of WNV infection in the resident horse population in Eastern Germany and showed that seroprevalence was higher in counties with previously registered equine WNV infections.
Vaccines against Major Poultry Viral Diseases: Strategies to Improve the Breadth and Protective Efficacy
Authors: Ravikumar Rajamanonmani , Chan Janlin , Prabakaran Mookkan
Published: May 2022

The poultry industry is the largest source of meat and eggs for human consumption worldwide. However, viral outbreaks in farmed stock are a common occurrence and a major source of concern for the industry. Mortality and morbidity resulting from an outbreak can cause significant economic losses with subsequent detrimental impacts on the global food supply chain. Mass vaccination is one of the main strategies for controlling and preventing viral infection in poultry. The development of broadly protective vaccines against avian viral diseases will alleviate selection pressure on field virus strains and simplify vaccination regimens for commercial farms with overall savings in husbandry costs. With the increasing number of emerging and re-emerging viral infectious diseases in the poultry industry, there is an urgent need to understand the strategies for broadening the protective efficacy of the vaccines against distinct viral strains. The current review provides an overview of viral vaccines and vaccination regimens available for common avian viral infections, and strategies for developing safer and more efficacious viral vaccines for poultry.
Mortality in SARS-CoV-2 Hospitalized Patients Treated with Remdesivir: A Nationwide, Registry-Based Study in Italy
Authors: Russo Pierluigi , Tacconelli Evelina , Olimpieri Pier Paolo , Celant Simone , Colatrella Antonietta , Tomassini Luca , Palù Giorgio
Published: May 2022

Remdesivir is the first drug approved for treatment of COVID-19 but current evidence for recommending its use for the treatment of moderate-to-severe disease is still controversial among clinical guidelines. We performed a nationwide, registry-based study including all Italian hospitalized patients with COVID-19 treated with remdesivir to assess the impact of major confounders on crude 15-day and 29-day mortality. Mortality was calculated using the Kaplan–Meier estimator and the Cox proportional-hazards model was applied to analyze the risks by patient’s baseline features. In total, 16,462 patients treated with remdesivir from 29 October 2020 to 17 December 2020 were entered in the study. Crude 15-day and 29-day mortality were 7.1% (95% CI, 6.7–7.5%) and 11.7% (95% CI, 11.2–12.2%), respectively. Being treated within two days of admission reduced the risk of death by about 40% (HR 1.4, 95% CI, 1.2–1.6). Results from the largest cohort of remdesivir-treated patients suggests that mortality in SARS-CoV-2 hospitalized patients is substantially influenced by the days between SARS-CoV-2 diagnosis and drug prescription. Current recommendations and future clinical trials for remdesivir alone or in combination should carefully consider the target population and timing for best efficacy of treatment.
Air Quality in Dental Care Facilities: Update to Current Management and Control Strategies Implementing New Technologies: A Comprehensive Review
Authors: Tzoutzas Ioannis , Karoussis Ioannis , Maltezou Helena C.
Published: May 2022

The quality of indoor air in healthcare facilities, with an emphasis on dental offices, attracted the attention of the scientific community in the late 1960s. Since then, it has become evident that the indoor air quality is critical in modern dental care facilities for limiting the spread of airborne infections, including vaccine-preventable diseases, and a key component of safety for healthcare personnel and patients. In the past decades, the role of indoor air quality has also been recognized in non-healthcare facilities, given the increasing time spent indoors by humans. During the provision of dental care services, mainly in the field of restorative dentistry, high-speed dental handpieces emitting air and water are used, producing large quantities of aerosol and hovering inside the operations area. In modern dental offices, new devices emitting air/powder for cavities improvement and cleaning as well as for periodontal prophylactic cleaning and aesthetics are used. In addition, a new therapeutic protocol for the removal of bacterial biofilm, targeting treatment for peri-implant diseases and conditions using air-abrasive decontamination technology, has been introduced in daily dental practice. The aim of this non-systemic review is to present the current state of knowledge on the nature and dynamics of air splatters and to provide an update to management and control strategies in dental care facilities, focusing on air purification and ultraviolet devices proposed and used. The findings arising from the limited number of related published articles documenting the reduction in levels of particular matter 2.5 (PM2.5), PM10 and volatile organic compounds, allow us to conclude that the continuous operation of air purifiers during and after treatment, contributes considerably to the improvement of the indoor air quality in dental care facilities. Moreover, the utilization of air purifiers is highly recommended in dental practice to mitigate spread of infections, including vaccine-preventable diseases. Frequent cleaning and maintenance of the purifier sieves and filters and frequent renovation of the indoor air through physical ventilation by mean of open windows is imperative. More research on environmental contamination and particularly on viral contamination under real dental care conditions is needed.
Routine Immunization Programs for Children during the COVID-19 Pandemic in Ecuador, 2020—Hidden Effects, Predictable Consequences
Authors: Suárez-Rodríguez Gianina Lizeth , Salazar-Loor José , Rivas-Condo Jackson , Rodríguez-Morales Alfonso J. , Navarro Juan-Carlos , Ramírez-Iglesias José Rubén
Published: May 2022

The COVID-19 pandemic has led to a global disruption of several services, including routine immunizations. This effect has been described in several countries, but there are few detailed studies in Latin America and no reports in Ecuador. Therefore, this work aims to quantify the reduction in routine immunizations for infants during the 2020 COVID-19 pandemic in Ecuador. 2018, 2019, and 2020 data were obtained from the Ministry of Health, Ecuador. The number of doses and the extent of immunization coverage was descriptively compared for four vaccines: rotavirus (ROTA), poliovirus (PV), pneumococcal (PCV), and pentavalent (PENTA) vaccines. There was no significant difference in doses applied during the 2018 and 2019 years. However, a significant (p < 0.05) drop of 137,000 delivered doses was observed in 2020 compared to the pre-pandemic years. Reductions in the percentage of coverage were more pronounced for the PENTA vaccine (17.7%), followed by PV (16.4%), ROTA (12%), and PCV vaccines (10.7%). Spatial analysis shows a severe impact on vaccination coverage on provinces from the Coast and Highland regions of the country. The pandemic has significantly impacted the immunization programs for infants across Ecuador. This retrospective analysis shows an urgent need to protect vulnerable zones and populations during public health emergencies.
A Single Dose of ChAdOx1 nCoV-19 Vaccine Elicits High Antibody Responses in Individuals with Prior SARS-CoV-2 Infection Comparable to That of Two-Dose-Vaccinated, SARS-CoV-2-Infection-Naïve Individuals: A Longitudinal Study in Ethiopian Health Workers
Authors: Gelanew Tesfaye , Mulu Andargachew , Abebe Markos , Bates Timothy A. , Wassie Liya , Teferi Mekonnen , Fentahun Dessalegn , Alemu Aynalem , Tamiru Frehiwot , Assefa Gebeyehu , Bayih Abebe Genetu , Tafesse Fikadu G. , Mihret Adane , Abdissa Alemseged
Published: May 2022

Single-dose COVID-19 vaccines, mostly mRNA-based vaccines, are shown to induce robust antibody responses in individuals who were previously infected with SARS-CoV-2, suggesting the sufficiency of a single dose for those individuals in countries with limited vaccine supply. However, these important data are limited to developed nations. We conducted a prospective longitudinal study among Ethiopian healthcare workers who received a ChAdOx1 nCoV-19 vaccine. We compared the geometric mean titers (GMTs) of the SARS-CoV-2 receptor-binding domain (RBD)-specific IgG antibodies in 39 SARS-CoV-2 naïve participants and 24 participants previously infected with SARS-CoV-2 (P.I.), who received two doses of ChAdOx1 nCoV-19 vaccine across the two post-vaccination time points (at 8 to 12 weeks post single dose and two dose vaccinations). We noted that the GMT (1632.16) in naïve participants at 8–12 weeks post first dose were comparable to the GMT (1674.94) observed in P.I. participants prior to vaccination. Interestingly, P.I. participants had significantly higher antibody titers compared to naïve participants, after both the first (GMT, 4913.50 vs. 1632.16) and second doses (GMT, 9804.60 vs. 6607.30). Taken together, our findings show that a single ChAdOx1 nCoV-19 dose in previously SARS-CoV-2 infected individuals elicits similar, if not higher, antibody responses to those of two-dose-vaccinated naïve individuals.
Vaccines against Drug Abuse—Are We There Yet?
Authors: Bloom Benedict T. , Bushell Mary-Jessimine
Published: May 2022

Background: Drug abuse is a worldwide problem that is detrimental to public health. The potential for drug abuse extends to both legal and illicit drugs. Drawbacks associated with current treatments include limited effectiveness, potential side effects and, in some instances, the absence of or concerns with approved therapy options. A significant amount of clinical research has been conducted investigating immunotherapy as a treatment option against drug abuse. Vaccines against drug abuse have been the main area of research, and are the focus of this review. Methods: An extensive search using “EBSCOhost (Multiple database collection)” with all 28 databases enabled (including “Academic Search Ultimate”, “CINAHL Plus with Full Text”, and MEDLINE), interrogation of the ClinicalTrials.gov website, and searches of individual clinical trial registration numbers, was performed in February and March of 2022. This search extended to references within the obtained articles. Results: A total of 23 registered clinical trials for treating drug abuse were identified: 15 for treatment of nicotine abuse (all vaccine-based trials), 6 against cocaine abuse (4 were vaccine-based trials and 2 were metabolic-enzyme-based trials), 1 against methamphetamine abuse (a monoclonal-antibody-based trial), and 1 multivalent opioid treatment (vaccine-based trial). As indicated on the ClinicalTrials.gov website (Home—ClinicalTrials.gov), the status of all but two of these trials was “Completed”. Phase 3 clinical trials were completed for vaccine treatments against nicotine and cocaine abuse only. Conclusion: Evidence in the form of efficacy data indicates that vaccines are not an option for treating nicotine or cocaine abuse. Efficacy data are yet to be obtained through completion of clinical trials for vaccines against opioid abuse. These findings align with the absence of regulatory approval for any of these treatments. This review further highlights the need for novel treatment strategies in instances where patients do not respond to current treatments, and while the search for efficacious vaccine-based treatments continues.
Execution and Design of an Anti HPIV-1 Vaccine with Multiple Epitopes Triggering Innate and Adaptive Immune Responses: An Immunoinformatic Approach
Authors: Naveed Muhammad , Yaseen Allah Rakha , Khalid Hira , Ali Urooj , Rabaan Ali A. , Garout Mohamed , Halwani Muhammad A. , Al Mutair Abbas , Alhumaid Saad , Al Alawi Zainab , Alhashem Yousef N. , Ahmed Naveed , Yean Chan Yean
Published: May 2022

Human Parainfluenza Virus (HPIV) Type-1, which is an anti-sense ribonucleic acid (RNA) virus belonging to the paramyxoviridae family, induces upper and lower respiratory tract infections. The infections caused by the HPIV Type-1 virus are usually confined to northwestern regions of America. HPIV-1 causes infections through the virulence of the hemagglutinin-neuraminidase (HN) protein, which plays a key role in the attachment of the viral particle with the host’s receptor cells. To the best of our knowledge, there is no effective antiviral drugs or vaccines being developed to combat the infection caused by HPIV-1. In the current study, a multiple epitope-based vaccine was designed against HPIV-1 by taking the viral HN protein as a probable vaccine candidate. The multiple epitopes were selected in accordance with their allergenicity, antigenicity and toxicity scoring. The determined epitopes of the HN protein were connected simultaneously using specific conjugates along with an adjuvant to construct the subunit vaccine, with an antigenicity score of 0.6406. The constructed vaccine model was docked with various Toll-like Receptors (TLRs) and was computationally cloned in a pET28a (+) vector to analyze the expression of vaccine sequence in the biological system. Immune stimulations carried out by the C-ImmSim Server showed an excellent result of the body’s defense system against the constructed vaccine model. The AllerTop tool predicted that the construct was non-allergen with and without the adjuvant sequence, and the VaxiJen 2.0 with 0.4 threshold predicted that the construct was antigenic, while the Toxinpred predicted that the construct was non-toxic. Protparam results showed that the selected protein was stable with 36.48 instability index (II) scores. The Grand average of Hydropathicity or GRAVY score indicated that the constructed protein was hydrophilic in nature. Aliphatic index values (93.53) confirmed that the construct was thermostable. This integrated computational approach shows that the constructed vaccine model has a potential to combat laryngotracheobronchitis infections caused by HPIV-I.
Confidence in a Vaccine against COVID-19 among Registered Nurses in Barcelona, Spain across Two Time Periods
Authors: Palma David , Hernández Anna , Picchio Camila A. , Jodar Glòria , Galbany-Estragués Paola , Simón Pere , Guillaumes Montserrat , Diez Elia , Rius Cristina
Published: May 2022

Objective: To report the vaccine hesitancy (VH) for a vaccine against COVID-19 in registered nurses in Barcelona, with measurements taken at two stages, prior to the vaccination campaign and once 75% vaccination coverage had been reached. Methods: A self-completed online survey was administered in December 2020 and again in July 2021 through the College of Nurses of Barcelona. It measured the prevalence of VH against a government-approved vaccine recommended by their employer, their intention to be vaccinated, perceptions of disease risk and vaccine protection, attitudes and beliefs to vaccination and social norm. Bivariate analysis according to VH and application time are presented. Results: 2430 valid responses were obtained in the first measurement and 2027 in the second. At both times, 86% were women and 69% worked mainly in the public sector. Prior to the vaccine availability, VH was 34.2%, decreasing to 17.9%. Risk perceptions were significantly lower in those with VH compared to non-VH, in all groups studied and at both times, while safety and efficacy perceptions increased in all groups, significantly less in VH. The greatest benefit of the COVID-19 vaccine is perceived by pharmaceutical companies. VH nurses perceived a more hesitant social environment. Conclusion: As the vaccination was rolled out, VH in nurses declined, with time improving the confidence in the safety and efficacy of the vaccines. Risk perceptions also decreased over time, except for the perception of severity in HCW where it increased. Trust in institutions impacts trust in vaccines.
Neutralizing Antibodies Response against SARS-CoV-2 Variants of Concern Elicited by Prior Infection or mRNA BNT162b2 Vaccination
Authors: Bonura Floriana , Genovese Dario , Amodio Emanuele , Calamusa Giuseppe , Sanfilippo Giuseppa Luisa , Cacioppo Federica , Giammanco Giovanni Maurizio , De Grazia Simona , Ferraro Donatella
Published: May 2022

In order to determine the humoral protective response against SARS-CoV-2, the vaccine-induced and naturally induced neutralizing antibodies (NtAbs) responses against SARS-CoV-2 variants circulating in Italy through in vitro live virus neutralization assay were evaluated. A total of 39 SARS-CoV-2 recovered subjects (COVID-19+) and 63 subjects with a two-dose cycle of the BNT16262 vaccine were enrolled. A single serum sample was tested for COVID-19+ at 35–52 days post-positive swab, while vaccinees blood samples were taken at one (V1) and at three months (V3) after administration of the second vaccine dose. Significantly higher NtAb titers were found against B.1 and Alpha in both COVID-19+ and vaccinees, while lower NtAb titers were detected against Delta, Gamma, and Omicron variants. A comparison between groups showed that NtAb titers were significantly higher in both V1 and V3 than in COVID-19+, except against the Omicron variant where no significant difference was found. COVID-19+ showed lower neutralizing titers against all viral variants when compared to the vaccinees. Two-dose vaccination induced a sustained antibody response against each analyzed variant, except for Omicron. The evolution process of SARS-CoV-2, through variants originating from an accumulation of mutations, can erode the neutralizing effectiveness of natural and vaccine-elicited immunity. Therefore, a need for new vaccines should be evaluated to contain the ongoing pandemic.
An Integrative Analysis of the Immune Features of Inactivated SARS-CoV-2 Vaccine (CoronaVac)
Authors: Jiang Zhujun , Lin Haishuang , Zhang Haoran , Shi Ningning , Zheng Zhetao , Dong Liangzhen , Yang Yuelin , Xia Qing
Published: May 2022

Currently, an inactivated vaccine has been widely used with encouraging results as a prophylactic agent against COVID-19 infection, which is caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and its variants. However, in vitro SARS-CoV-2 vaccine-specific immune features remain elusive, hindering the promotion of a third dose of the vaccine. Here, we present a detailed in vitro immune cellular response and large-scale multi-omics analysis for peripheral blood mononuclear cells (PBMCs) from participants vaccinated with CoronaVac (Sinovac Life Sciences, Beijing, China) and recovered participants from COVID-19. The mean titers of SARS-CoV-2 serum-neutralizing antibodies were significantly increased after the boosting immunization (Day 45) compared to the unimmunized state. We observed that type-1 helper T cells (Th1) tended to dominate after the first dose of vaccine, while humoral immune responses became dominant after the second dose due to the activation of type-2 helper T cell (Th2), memory B cells, and plasmablasts. T follicular helper cells (Tfh) involved in antibody production were activated after the first dose and were maintained for the observed time points. Single-cell RNA sequencing of PBMCs revealed specific changes in cell compositions and gene expression in immunized participants. Multi-omics analysis also demonstrated that CoronaVac-specific serum proteins, plasma metabolites, and plasma lipid changes were skewed to those changes in convalescent patients. Collectively, we provide a comprehensive understanding of CoronaVac-specific in vitro immune features.
Vaccine Response in the Immunocompromised Patient with Focus on Cellular Immunity
Authors: Bahrs Christina , Harrison Nicole
Published: May 2022

During the last few years, we have experienced a shift in how we evaluate the effectiveness of vaccines [...]
Assessment of the Potential of Coordinating Two Interacting Monitoring Networks within the Lerma-Santiago Hydrologic System in Mexico
Authors: Gradilla-Hernández Misael Sebastián , Díaz-Vázquez Diego , Yebra-Montes Carlos , del Castillo Alberto Fernández , Shear Harvey , Garcia-Gonzalez Alejandro , de Anda José , Mazari-Hiriart Marisa
Published: May 2022

Water quality monitoring networks in the global south often display inefficiencies because monitoring strategies are frequently designed based on subjective professional judgments to define the temporal and spatial attributes of the networks, leading to poor cost–benefit relationships. The Lerma-Santiago Hydrological System (LSHS) in Mexico currently experiences severe environmental degradation caused by uncontrolled pollutant emissions from urban centers, agricultural, livestock, and industrial activities settled in the basin. While both the national and state authorities monitor this hydrological system, there has never been an effort to assess the monitoring efficiency of these two networks. The aim of the present study was to assess through multivariate statistical analyses the potential for coordination between these two interacting networks. For this purpose, two independent large water quality datasets with temporal and spatial attributes measured by two different authorities (the federal and the state) were used to identify those sites where coordination should be rationalized and those parameters that should continue to be monitored. The case study herein presented highlights the duplication in efforts to monitor surface water quality in the Lerma-Santiago hydrologic system, which implies a lack of coordination between the authorities and shows that water quality monitoring networks have not been reassessed since they were first implemented. Furthermore, using the case study of the Lerma-Santiago in Mexico, we expanded on various deficiencies, such as the use of different sampling frequencies and analytical methods by the authorities and inefficient communication among federal and state authorities. This study has revealed a large potential for coordinating two water quality monitoring networks (WQMN) in the Lerma-Santiago Hydrological System and a methodological approach that may be used to assess this potential. Coordination strategies for WQMNs can lead to significant cost reductions, extended network reach, and higher overall data quality in developing countries with limited financial resources and technical capabilities.
A Prediction Model of Labyrinth Emitter Service Duration (ESD) under Low-Quality (Sand-Laden Water) Irrigation
Authors: Wang Hui , Ling Gang , Wang Wene , Hu Xiaotao , Gao Xijian
Published: May 2022

The reasonable evaluation of emitter service duration and appropriate emitter selection have become an important way to improve the efficiency of drip irrigation systems, and also provide a basis for the wide application of drip irrigation technology in agricultural and landscape irrigation. During field irrigation, both irrigation uniformity (CU) and relative average flow (Dra) play crucial roles in crop growth, so it is not appropriate to evaluate emitters based on one of these factors alone. In this study, a new comprehensive index for measuring the operating life of emitters—the emitter service duration (ESD) was established for selecting emitter products in the field. The indoor drip irrigation experiment was carried out under nine kinds of sand-laden water, and the emitters’ service duration, based on irrigation uniformity and emitter flow, was tested. By analyzing the individual effects and the comprehensive effects of them, the comprehensive measurement index of the ESD was established and the Pearson bivariate correlation analysis was used to explore the influencing factors. The results showed that the lower the quality of the irrigation water, the smaller the value of the ESD, which meant that the emitters were more likely to be blocked. Different irrigation water sources had different effects on the ESD, which were mainly caused by the characteristic size. Two dimensionless characteristic parameters (W/D and A1/2/L) are significantly correlated with ESD. Based on W/D and A1/2/L, the ESD prediction model was obtained and the accuracy could reach 86%. It could provide an accurate method for selecting emitters under different water source conditions, which is beneficial for the safe, efficient, and long-term operation of a drip irrigation systems using a low-quality water source.
Mid- to Long-Term Runoff Prediction Based on Deep Learning at Different Time Scales in the Upper Yangtze River Basin
Authors: Ren Yuanxin , Zeng Sidong , Liu Jianwei , Tang Zhengyang , Hua Xiaojun , Li Zhenghao , Song Jinxi , Xia Jun
Published: May 2022

Deep learning models are essential tools for mid- to long-term runoff prediction. However, the influence of the input time lag and output lead time on the prediction results in deep learning models has been less studied. Based on 290 schemas, this study specified different time lags by sliding windows and predicted the runoff process by RNN (Recurrent Neural Network), LSTM (Long–short-term Memory), and GRU (Gated Recurrent Unit) models at five hydrological stations in the upper Yangtze River during 1980–2018 at daily, ten-day, and monthly scales. Different models have different optimal time lags; therefore, multiple time lags were analyzed in this paper to find out the relationship between the time intervals and the accuracy of different river runoff predictions. The results show that the optimal time-lag settings for the RNN, LSTM, and GRU models in the daily, ten-day, and monthly scales were 7 days, 24 ten days, 27 ten days, 24 ten days, 24 months, 27 months, and 21 months, respectively. Furthermore, with the increase of time lags, the simulation accuracy would stabilize after a specific time lag at multiple time scales of runoff prediction. Increased lead time was linearly related to decreased NSE at daily and ten-day runoff prediction. However, there was no significant linear relationship between NSE and lead time at monthly runoff prediction. Choosing the smallest lead time could have the best prediction results at different time scales. Further, the RMSE of the three models revealed that RNN was inferior to LSTM and GRU in runoff prediction. In addition, RNN, LSTM, and GRU models could not accurately predict extreme runoff events at different time scales. This study highlights the influence of time-lag setting and lead-time selection in the mid- to long-term runoff prediction results for the upper Yangtze River basin. It is recommended that researchers should evaluate the effect of time lag before using deep learning models for runoff prediction, and to obtain the best prediction, the shortest lead-time length can be chosen as the best output for different time scales.