bluuebunny/crossref_metadata_2025 huggingface dataset:
Exposure to Polypropylene Microplastics via Oral Ingestion Induces Colonic Apoptosis and Intestinal Barrier Damage through Oxidative Stress and Inflammation in Mice
Authors: Jia Rui , Han Jie , Liu Xiaohua , Li Kang , Lai Wenqing , Bian Liping , Yan Jun , Xi Zhuge
Published: January 2023

Extensive environmental pollution by microplastics has increased the risk of human exposure to plastics. However, the biosafety of polypropylene microplastics (PP-MPs), especially of PP particles < 10 μm, in mammals has not been studied. Thus, here, we explored the mechanism of action and effect of exposure to small and large PP-MPs, via oral ingestion, on the mouse intestinal tract. Male C57BL/6 mice were administered PP suspensions (8 and 70 μm; 0.1, 1.0, and 10 mg/mL) for 28 days. PP-MP treatment resulted in inflammatory pathological damage, ultrastructural changes in intestinal epithelial cells, imbalance of the redox system, and inflammatory reactions in the colon. Additionally, we observed damage to the tight junctions of the colon and decreased intestinal mucus secretion and ion transporter expression. Further, the apoptotic rate of colonic cells significantly increased after PP-MP treatment. The expression of pro-inflammatory and pro-apoptosis proteins significantly increased in colon tissue, while the expression of anti-inflammatory and anti-apoptosis proteins significantly decreased. In summary, this study demonstrates that PP-MPs induce colonic apoptosis and intestinal barrier damage through oxidative stress and activation of the TLR4/NF-κB inflammatory signal pathway in mice, which provides new insights into the toxicity of MPs in mammals.
Nonlinear Associations between Blood Cadmium Concentration and Thyroid Hormones According to Smoking Status in Korean Adults: The Korea National Health and Nutrition Examination Survey (KNHANES)
Authors: Kim Byungmi , Rhie Minshik , Park Sunhee , Kim Hyo-Seon , Kwon Jeoung A
Published: January 2023

Research on the association between blood cadmium (BCd) exposure and thyroid hormone levels in the general population has been inconclusive. Therefore, we examined the associations between BCd and thyroid hormones according to smoking status in Korean adults (N = 1170, Men = 722, Women = 448) using multiple linear regression and restricted cubic splines analysis with data from the Korean National Health and Nutrition Examination Survey (2013). The geometric mean of BCd was 0.74 μg/L in all study participants and was higher in smokers (1.01 μg/L) than in nonsmokers (0.65 μg/L). Restricted cubic splines analysis revealed nonlinear trends between BCd and free thyroxine in smokers (p for nonlinearity = 0.02). By contrast, there were no significant associations between BCd and thyroid hormones in either men or women. In conclusion, nonlinear associations may exist between BCd and free thyroxine in smokers. Our study provides empirical support for the future formulation of an acceptable concentration range of BCd and offers a new concept for preventing thyroid problems.
Analysis of Cadmium Retention Mechanisms by a Smectite Clay in the Presence of Carbonates
Authors: Missana Tiziana , Alonso Ursula , Mayordomo Natalia , García-Gutiérrez Miguel
Published: January 2023

Cadmium (Cd) is a toxic heavy metal with very low permissible exposure limits and is, thus, a very dangerous pollutant for the environment and public health and is considered by the World Health Organisation as one of the ten chemicals of major public concern. Adsorption onto solid phases and (co)precipitation processes are the most powerful mechanisms to retain pollutants and limit their migration; thus, the understanding of these processes is fundamental for assessing the risks of their presence in the environment. In this study, the immobilisation of Cd by smectite clay has been investigated by batch sorption tests, and the experimental data were interpreted with a thermodynamic model, including cation exchange and surface complexation processes. The model can describe the adsorption of Cd in smectite under a wide range of experimental conditions (pH, ionic strength, and Cd concentration). Under the conditions analysed in this study, the precipitation of otavite (CdCO3) is shown to have a limited contribution to Cd immobilisation.
Determination of Parabens and Their Metabolites in Seminal Plasma from Chinese Men by Ultra High Performance Liquid Chromatography Tandem Mass Spectrometry (UPLC-MS/MS)
Authors: Dai Jing , Zhang Linyuan , Xu Jianfeng , Peng Fangda , Wu Zhijun , Fu Longlong , Guo Ying , Chang Bing , Lu Wenhong , Ding Chunguang
Published: January 2023

Parabens are endocrine-disrupting chemicals (EDCs) that have estrogen-like activities and may cause male reproductive disorders. Here, we developed a method for the simultaneous determination of four parabens (MeP, EtP, n-PrP, n-BuP) and two metabolites (4-HB and 3,4-DHB) in human seminal plasma by UPLC-MS/MS. The method was used to analyze 144 seminal plasma samples from Chinese males. MeP, EtP, n-PrP, and 4-HB were the dominant compounds. MeP, EtP, and n-PrP were significantly correlated to each other. In addition, 4-HB was significantly correlated to MeP, EtP, n-PrP, and 3,4-DHB, respectively. The results provide direct evidence that parabens and their metabolites are widely distributed in the male reproductive system. The study presents the paraben metabolites levels in human seminal plasma for the first time.
The Emerging Role of Autophagy as a Target of Environmental Pollutants: An Update on Mechanisms
Authors: Rahman Md. Ataur , Rahman Md Saidur , Parvez Md. Anowar Khasru , Kim Bonglee
Published: January 2023

Autophagy is an evolutionarily conserved cellular system crucial for cellular homeostasis that protects cells from a broad range of internal and extracellular stresses. Autophagy decreases metabolic load and toxicity by removing damaged cellular components. Environmental contaminants, particularly industrial substances, can influence autophagic flux by enhancing it as a protective response, preventing it, or converting its protective function into a pro-cell death mechanism. Environmental toxic materials are also notorious for their tendency to bioaccumulate and induce pathophysiological vulnerability. Many environmental pollutants have been found to influence stress which increases autophagy. Increasing autophagy was recently shown to improve stress resistance and reduce genetic damage. Moreover, suppressing autophagy or depleting its resources either increases or decreases toxicity, depending on the circumstances. The essential process of selective autophagy is utilized by mammalian cells in order to eliminate particulate matter, nanoparticles, toxic metals, and smoke exposure without inflicting damage on cytosolic components. Moreover, cigarette smoke and aging are the chief causes of chronic obstructive pulmonary disease (COPD)-emphysema; however, the disease’s molecular mechanism is poorly known. Therefore, understanding the impacts of environmental exposure via autophagy offers new approaches for risk assessment, protection, and preventative actions which will counter the harmful effects of environmental contaminants on human and animal health.
Cytotoxicity and Oxidative Stress Effects of Indene on Coelomocytes of Earthworm (Eisenia foetida): Combined Analysis at Cellular and Molecular Levels
Authors: Huo Chengqian , Zhao Qiang , Liu Rutao , Li Xiangxiang , He Falin , Jing Mingyang , Wan Jingqiang , Zong Wansong
Published: January 2023

Indene (IND) is a kind of important aromatic hydrocarbon that is extracted from coal tar and has important applications in industry and biology. In the process of production and utilization, it is easy to enter the soil and produce toxic effects on the soil or organisms. The earthworm is an important organism in the soil. The toxicity of indene on earthworm coelomocytes is rarely studied, and the oxidative stress effects of IND on earthworm coelomocytes remain unclear. In this study, coelomocytes from earthworms and antioxidant enzymes were selected as the research targets. In addition, IND caused oxidative stress, and its related toxic effects and mechanisms were systematically studied and evaluated at the cellular and molecular levels. The results showed that IND destroyed the redox balance in earthworm coelomocytes, and the large accumulation of reactive oxygen species (ROS) significantly inhibited the activities of the antioxidant system, including superoxide dismutase (SOD), catalase (CAT), and glutathione (GSH), and caused lipid peroxidation and membrane permeability changes, resulting in a decrease in cell viability to 74.5% of the control group. At the molecular level, IND was bound to SOD by the arene-H bond, and the binding constant was 4.95 × 103. IND changed the secondary structure of the SOD and led to a loosening of the structure of the SOD peptide chain. Meanwhile, IND caused SOD fluorescence sensitization, and molecular simulation showed that IND was mainly bound to the junction of SOD subunits. We hypothesized that the changes in SOD structure led to the increase in SOD activity. This research can provide a scientific basis for IND toxicity evaluation.
Dengue in Pregnancy: A Southeast Asian Perspective
Authors: Chong Vanessa , Tan Jennifer Zi Ling , Arasoo Valliammai Jayanthi Thirunavuk
Published: January 2023

Dengue cases have been rising in recent years. In 2019 alone, over 658,301 of the 5.6 million reported cases originated from Southeast Asia (SEA). Research has also shown detrimental outcomes for pregnant infected women. Despite this, existing literature describing dengue’s effects on pregnancy in SEA is insufficient. Through this narrative review, we sought to describe dengue’s effects on pregnancy systemically and emphasize the existing gaps in the literature. We extensively searched various journals cited in PubMed and Ovid Medline, national clinical practice guidelines, and governmental reports. Dengue in pregnancy increases the risk of pre-eclampsia, Dengue Hemorrhagic Fever (DHF), fetal distress, preterm delivery, Caesarean delivery, and maternal mortality. Vertical transmission, intrauterine growth restriction, and stillbirth are possible sequelae of dengue in fetuses. We found that trimester-specific physiological impacts of dengue in pregnancy (to both mother and child) and investigations and management methods demanded further research, especially in the SEA region.
A Qualitative Study on the Implementation of the Workplace TB Program in the Philippines: Challenges and Way Forward
Authors: Roxas Evalyn A. , Fadrilan-Camacho Vivien Fe F. , Lota Maria Margarita M. , Hernandez Paul Michael R. , Agravante Adrian Paul M. , Loterio Loisse Mikaela M. , Arevalo Micaela J. , Maglalang Richelle Liza F. , Lumangaya Carlo R. , Belizario Vicente Y.
Published: January 2023

Tuberculosis (TB) is a chronic infectious disease that remains to be a primary health concern globally. The Philippines is among the top TB-burdened countries. Workplace TB prevention and control programs are essential to ensure the health and safety of workers and economic security. There remains a knowledge gap regarding the Philippine workplace TB prevention and control program implementation. This qualitative study involving key informant interviews reviewed the implementation of the workplace TB program in selected companies in a high TB burden region in Eastern Philippines. Results were presented under four themes in accordance with the components of the workplace TB policy: preventive strategies, medical management, data recording and reporting, and social policy. Various good practices, opportunities, and challenges in the implementation of the workplace TB program were identified. There is a need to strengthen the enforcement of policy across different components. Compliance with guidelines on preventive strategies and recording and reporting schemes needs to be intensified. Coordination across different levels and agencies may also be enhanced to allow more efficient implementation. Increased awareness of corporate decision-makers may improve company ownership of the program leading to improved implementation while increased awareness of employees on their rights and entitlements may likewise enhance compliance.
On Statistical Fluctuations in Collective Flows
Authors: Qian Wei-Liang , Lin Kai , Ye Chong , Li Jin , Pan Yu , Yue Rui-Hong
Published: January 2023

In relativistic heavy-ion collisions, event-by-event fluctuations are known to have non-trivial implications. Even though the probability distribution is geometrically isotropic for the initial conditions, the anisotropic εn still differs from zero owing to the statistical fluctuations in the energy profile. On the other hand, the flow harmonics extracted from the hadron spectrum using the multi-particle correlators are inevitably subjected to non-vanishing variance due to the finite number of hadrons emitted in individual events. As one aims to extract information on the fluctuations in the initial conditions via flow harmonics and their fluctuations, finite multiplicity may play a role in interfering with such an effort. In this study, we explore the properties and impacts of such fluctuations in the initial and final states, which both notably appear to be statistical ones originating from the finite number of quanta of the underlying system. We elaborate on the properties of the initial-state eccentricities for the smooth and event-by-event fluctuating initial conditions and their distinct impacts on the resulting flow harmonics. Numerical simulations are performed. The possible implications of the present study are also addressed.
Editorial for the Special Issue “Recent Advances in Neutrino Physics: From Theory to Experiments”
Authors: Luciano Giuseppe Gaetano , Blasone Massimo
Published: January 2023

Among all the known particles in our Universe, neutrinos are definitely the most elusive and mysterious [...]
The Long Journey of ICARUS: From the LAr-TPC Concept to the First Full-Scale Detector
Authors: Menegolli Alessandro
Published: January 2023

The Liquid Argon Time Projection Chamber (LAr-TPC) technology was conceived at the end of the 1970s as a way to combine the excellent spatial and calorimetric performance of the traditional bubble chambers with the electronic read-out of the TPCs, obtaining the so-called “electronic bubble chambers”. This technology was intended to be applied in particular to neutrino physics as an alternative to Ring Water Cherenkov detectors. The main technological issues of such an innovative technique were investigated from the very beginning within the ICARUS program, with staged R&D starting from prototypes of increasing mass to arrive, at the end of 1990s, at the largest LAr-TPC detector ever built at that time: ICARUS-T600, with almost 500 tons of active LAr. The successful operations of the ICARUS-T600 LAr-TPC in its more than twenty years of life, from the first run at surface in Pavia (Italy) in 2001 to the LNGS (Italy) underground run being exposed to the CNGS beam from CERN to Gran Sasso (2010–2013) and finally to the ongoing run at Fermilab (USA) for sterile neutrino searches (2020–), have demonstrated the huge potential of the LAr-TPC technique, paving the way to future larger LAr-TPCs detectors as DUNE.
Modulation of the Aryl Hydrocarbon Receptor Signaling Pathway Impacts on Junín Virus Replication
Authors: Pelaez Miguel Angel , Torti María Florencia , Alvarez De Lauro Aaron Ezequiel , Marquez Agostina Belén , Giovannoni Federico , Damonte Elsa Beatriz , García Cybele Carina
Published: January 2023

Junín virus (JUNV), a member of the family Arenaviridae, is the etiological agent of the Argentine hemorrhagic fever, an endemic disease in the rural region of Argentina lacking a specific chemotherapy. Aryl hydrocarbon receptor (AHR) is expressed in several mammalian tissues and has been indicated as a sensor of ligands from variable sources and a modulator of the cell immune response. Interestingly, recent studies have suggested that the activation or depression of the AHR signaling pathway may play a role in the outcome of diverse human viral infections. In the present report, the effect of the pharmacological modulation of AHR on JUNV in vitro infection was analyzed. An initial microarray screening showed that the AHR pathway was overexpressed in JUNV-infected hepatic cells. Concomitantly, the infection of Vero and Huh-7 cells with the JUNV strains IV4454 and Candid#1 was significantly inhibited in a dose-dependent manner by treatment with CH223191, a specific AHR antagonist, as detected by infectivity assays, real-time RT-PCR and immunofluorescence detection of viral proteins. Furthermore, the pro-viral role of AHR in JUNV infection appears to be independent of the IFN-I pathway. Our findings support the promising perspectives of the pharmacological modulation of AHR as a potential target for the control of AHF.
Clinical Utility of Quantitative HBV Core Antibodies for Solving Diagnostic Dilemmas
Authors: Lazarevic Ivana , Banko Ana , Miljanovic Danijela , Cupic Maja
Published: January 2023

The present-day management of hepatitis B virus (HBV) infection relies on constant and appropriate monitoring of viral activity, disease progression and treatment response. Traditional HBV infection biomarkers have many limitations in predicting clinical outcomes or therapy success. Quantitation of HBV core antibodies (qAnti-HBc) is a new non-invasive biomarker that can be used in solving multiple diagnostic problems. It was shown to correlate well with infection phases, level of hepatic inflammation and fibrosis, exacerbations during chronic infection and presence of occult infection. Further, the level of qAnti-HBc was recognised as predictive of spontaneous or therapy-induced HBeAg and HBsAg seroclearance, relapse after therapy discontinuation, re-infection after liver transplantation and viral reactivation upon immunosuppression. However, qAnti-HBc cannot be relied upon as a single diagnostic test to solve all dilemmas, and its diagnostic and prognostic power can be much improved when combined with other diagnostic biomarkers (HBV DNA, HBeAg, qHBsAg and anti-HBs antibodies). The availability of commercial qAnti-HBc diagnostic kits still needs to be improved. The comparison of results from different studies and definitions of universal cut-off values continue to be hindered because many methods are only semi-quantitative. The clinical utility of qAnti-HBc and the methods used for its measurement are the focus of this review.
Assessment and Diagnosis of HIV-Associated Dementia
Authors: Cornea Amalia , Lata Irina , Simu Mihaela , Rosca Elena Cecilia
Published: January 2023

The modern combined antiretroviral treatment (cART) for human immunodeficiency virus (HIV) infection has substantially lowered the incidence of HIV-associated dementia (HAD). The dominant clinical features include deficits in cognitive processing speed, concentration, attention, and memory. As people living with HIV become older, with high rates of comorbidities and concomitant treatments, the prevalence and complexity of cognitive impairment are expected to increase. Currently, the management of HAD and milder forms of HAND is grounded on the best clinical practice, as there is no specific, evidence-based, proven intervention for managing cognitive impairment. The present article acknowledges the multifactorial nature of the cognitive impairments found in HIV patients, outlining the current concepts in the field of HAD. Major areas of interest include neuropsychological testing and neuroimaging to evaluate CNS status, focusing on greater reliability in the exclusion of associated diseases and allowing for earlier diagnosis. Additionally, we considered the evidence for neurological involvement in severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection and the impact of the coronavirus (COVID-19) pandemic, with wider consequences to population health than can be attributed to the virus itself. The indirect effects of COVID-19, including the increased adoption of telehealth, decreased access to community resources, and social isolation, represent a significant health burden, disproportionately affecting older adults with dementia who have limited social networks and increased functional dependence on the community and health system. This synopsis reviews these aspects in greater detail, identifying key gaps and opportunities for researchers and clinicians; we provide an overview of the current concepts in the field of HAD, with suggestions for diagnosing and managing this important neurological complication, which is intended to be applicable across diverse populations, in line with clinical observations, and closely representative of HIV brain pathology.
An Estuarine Cyanophage S-CREM1 Encodes Three Distinct Antitoxin Genes and a Large Number of Non-Coding RNA Genes
Authors: Zheng Hongrui , Liu Yuanfang , Zhou Ruiyu , Liu Jihua , Xu Yongle , Chen Feng
Published: January 2023

Cyanophages play important roles in regulating the population dynamics, community structure, metabolism, and evolution of cyanobacteria in aquatic ecosystems. Here, we report the genomic analysis of an estuarine cyanophage, S-CREM1, which represents a new genus of T4-like cyanomyovirus and exhibits new genetic characteristics. S-CREM1 is a lytic phage which infects estuarine Synechococcus sp. CB0101. In contrast to many cyanomyoviruses that usually have a broad host range, S-CREM1 only infected the original host strain. In addition to cyanophage-featured auxiliary metabolic genes (AMGs), S-CREM1 also contains unique AMGs, including three antitoxin genes, a MoxR family ATPase gene, and a pyrimidine dimer DNA glycosylase gene. The finding of three antitoxin genes in S-CREM1 implies a possible phage control of host cells during infection. One small RNA (sRNA) gene and three cis-regulatory RNA genes in the S-CREM1 genome suggest potential molecular regulations of host metabolism by the phage. In addition, S-CREM1 contains a large number of tRNA genes which may reflect a genomic adaption to the nutrient-rich environment. Our study suggests that we are still far from understanding the viral diversity in nature, and the complicated virus–host interactions remain to be discovered. The isolation and characterization of S-CREM1 further our understanding of the gene diversity of cyanophages and phage–host interactions in the estuarine environment.
Repetitive Exposure to Bacteriophage Cocktails against Pseudomonas aeruginosa or Escherichia coli Provokes Marginal Humoral Immunity in Naïve Mice
Authors: Weissfuss Chantal , Wienhold Sandra-Maria , Bürkle Magdalena , Gaborieau Baptiste , Bushe Judith , Behrendt Ulrike , Bischoff Romina , Korf Imke H. E. , Wienecke Sarah , Dannheim Antonia , Ziehr Holger , Rohde Christine , Gruber Achim D. , Ricard Jean-Damien , Debarbieux Laurent , Witzenrath Martin , Nouailles Geraldine
Published: January 2023

Phage therapy of ventilator-associated pneumonia (VAP) is of great interest due to the rising incidence of multidrug-resistant bacterial pathogens. However, natural or therapy-induced immunity against therapeutic phages remains a potential concern. In this study, we investigated the innate and adaptive immune responses to two different phage cocktails targeting either Pseudomonas aeruginosa or Escherichia coli—two VAP-associated pathogens—in naïve mice without the confounding effects of a bacterial infection. Active or UV-inactivated phage cocktails or buffers were injected intraperitoneally daily for 7 days in C57BL/6J wild-type mice. Blood cell analysis, flow cytometry analysis, assessment of phage distribution and histopathological analysis of spleens were performed at 6 h, 10 days and 21 days after treatment start. Phages reached the lungs and although the phage cocktails were slightly immunogenic, phage injections were well tolerated without obvious adverse effects. No signs of activation of innate or adaptive immune cells were observed; however, both active phage cocktails elicited a minimal humoral response with secretion of phage-specific antibodies. Our findings show that even repetitive injections lead only to a minimal innate and adaptive immune response in naïve mice and suggest that systemic phage treatment is thus potentially suitable for treating bacterial lung infections.
Cardiac Arrhythmias in Post-COVID Syndrome: Prevalence, Pathology, Diagnosis, and Treatment
Authors: Huseynov Aydin , Akin Ibrahim , Duerschmied Daniel , Scharf Rüdiger E.
Published: January 2023

An increase in post-COVID patients with late sequelae of acute COVID-19 infection is emerging as an ongoing challenge for physicians and healthcare professionals. Since the beginning of the pandemic, it has rapidly become evident that the acute infection is not limited to the respiratory tract but that several organs, including the cardiovascular system, can be affected. Moreover, in a significant proportion of patients (ranging from about 10 to up to 50%) with former COVID-19, cardiopulmonary symptoms such as dyspnea, palpitations, restricted physical capacity, and cardiac arrhythmias can persist weeks and months after the acute SARS-CoV-2 infection. The spectrum of COVID-19-associated arrhythmias is rather wide, most likely due to various pathomechanisms. In this article, the prevalence of cardiac arrhythmias and underlying pathologies are reviewed, including direct myocardial injury and abnormal consequences with an impact on cardiac electric instability. The hyperinflammatory reaction of the host immune system is specifically considered. Moreover, several distinct rhythm disorders occurring in post-COVID patients are discussed with regard to their clinical management.
COVID-19 in a Pre-Omicron Era: A Cross-Sectional Immuno-Epidemical and Genomic Evaluation
Authors: Pagnossa Jorge Pamplona , Rodrigues Sarah de Oliveira , Oliveira Gabriel Ferrari de , Adnan Mohd , Aljaid Maryam Saud , Assis Isabela Bacelar de , Lima Alex Sandro Gomes , Patel Mitesh , Ogaly Hanan A. , Batiha Gaber El-Saber
Published: January 2023

The seventh human coronavirus was discovered and reported primarily in Wuhan, China. After intense seasons with repercussions in all areas of humanity, the pandemic demonstrates a new perspective. In Brazil, the pandemic concept had impacts in vast areas, including healthcare hospitals. This present study aims to describe and synthesize data from a determined period from the year 2021 that correlate the symptoms of passive and/or active patients for COVID-19 and their respective results of IgG/IgM serological tests in hospitals in the city of Cruzeiro, São Paulo, Brazil. The form had been applied to 333 people and obtained conclusive results and several symptoms were presented; in addition, asymptomatic cases were also analyzed and directed in the genomic study of variants of concern, as well as vaccination data in the study region.
The BNT162b2 mRNA COVID-19 Vaccine Increases the Contractile Sensitivity to Histamine and Parasympathetic Activation in a Human Ex Vivo Model of Severe Eosinophilic Asthma
Authors: Calzetta Luigino , Chetta Alfredo , Aiello Marina , Frizzelli Annalisa , Ora Josuel , Melis Enrico , Facciolo Francesco , Ippoliti Lorenzo , Magrini Andrea , Rogliani Paola
Published: January 2023

The BNT162b2 COVID-19 vaccine is composed of lipid-nanoparticles (LNP) containing the mRNA that encodes for SARS-CoV-2 spike glycoprotein. Bronchospasm has been reported as an early reaction after COVID-19 mRNA vaccines in asthmatic patients. The aim of this study was to investigate the acute impact of BNT162b2 in a human ex vivo model of severe eosinophilic asthma. Passively sensitized human isolated bronchi were challenged with the platelet-activating factor to reproduce ex vivo the hyperresponsiveness of airways of patients suffering from severe eosinophilic asthma. BNT162b2 was tested on the contractile sensitivity to histamine and parasympathetic activation via electrical field stimulation (EFS); some experiments were performed after mRNA denaturation. BNT162b2 increased the resting tone (+11.82 ± 2.27%) and response to histamine in partially contracted tissue (+42.97 ± 9.64%) vs. the control (p < 0.001); it also shifted the concentration-response curve to histamine leftward (0.76 ± 0.09 logarithm) and enhanced the response to EFS (+28.46 ± 4.40%) vs. the control. Denaturation did not significantly modify (p > 0.05) the effect of BNT162b2. BNT162b2 increases the contractile sensitivity to histamine and parasympathetic activation in hyperresponsive airways, a detrimental effect not related to the active component but to some excipient. A possible candidate for the bronchospasm elicited by BNT162b2 could be the polyethylene glycol/macrogol used to produce LNP.
Low-Grade Cervical Intraepithelial Neoplasia (CIN1) Evolution: Analysis of Opportunistic Preventive Vaccination Role
Authors: Gardella Barbara , Dominoni Mattia , Pasquali Marianna Francesca , Melito Chiara , Fiandrino Giacomo , Cesari Stefania , La Verde Marco , Spinillo Arsenio
Published: January 2023

Background: Low-grade cervical lesions have a high percentage of clearance in young women, even if 71–82% of low-grade intraepithelial lesion/atypical squamous cells of undetermined significance (LSIL/ASCUS) reported a High-Risk Human Papillomavirus (HR-HPV) infection, which correlates with an increased risk of Cervical Intraepithelial Neoplasia (CIN)2+. The immunogenic effect of the anti-HPV vaccine appears to be significant. The aim of the study is to evaluate the effect, two years after the diagnosis, of the anti-HPV preventive vaccination on patients with low-grade cervical lesions. Methods: We collected clinical, colposcopic, histological, and virological data from patients aged 21–45 years who attended the colposcopy service of the department of Obsetrics and Gynecology of IRCCS Foundation Policlinico San Matteo, Pavia, Italy. In the 2005–2019 period and had a low-grade pap-smear. Results: We enrolled 422 women consecutively, divided into two groups (vaccinated and not vaccinated) for the retrospective analysis. The rate of persistence and progression of CIN were higher in the not-vaccinated group (p = 0.019). The relative risk (RR) to develop CIN2+ during follow-up vs. the the CIN1 persistence was 1.005 (95% Confidence Interval—CI 0.961–1.051) vs. 0.994 (95% CI 0.994–1.018) for age, 3.472 (95% CI 1.066–11.320) vs. 1.266 (95% CI 0.774–2.068) for non-vaccinated, 0.299 (95% CI 0.088–1.018) vs. 0.518 (95% CI 0.242–1.109) for HIV status negative, respectively. Analyzing the time to negativity, the odds ratio (OR) was 1.012 (95% CI 1–1.024) for age and 1.591 (95% CI 1.223–2.069) for vaccination; on the other hand, considering the relationship between the time to negative and the HPV genotypes contained in the 9-valent HPV vaccines, the OR was 1.299 (95% CI 1.026–1.646) for at least one of these at recruitment and 0.631 (95% CI 0.471–0.846) at follow-up. Furthermore, the presence of at least one of the HPV genotypes targeted by the HPV nonavalent vaccine is a key indicator of the risk of progression to CIN2+: OR was 3.443 (95% CI 1.065–11.189) for the presence of at least one HPV genotype at enrollment and 5.011 (95% CI 1.899–13.224) for the presence of at least one HPV genotype at follow-up, respectively. Conclusions: We reported in a retrospective study the benefit of anti-HPV vaccination in promoting negativity and increasing low-grade cervical lesions regression.
Knowledge of Human Mpox (Monkeypox) and Attitude towards Mpox Vaccination among Male Sex Workers in China: A Cross-Sectional Study
Authors: Chen Yuanyi , Li Yuwei , Fu Leiwen , Zhou Xinyi , Wu Xinsheng , Wang Bingyi , Peng Xin , Sun Yinghui , Liu Qi , Lin Yi-Fan , Fan Yinguang , Jiang Hongbo , Meng Xiaojun , Zou Huachun
Published: January 2023

Background: Re-emerging human mpox (previously known as monkeypox) is spreading around the world. According to existing studies, the current mpox pandemic mainly affects men who have sex with men (MSM), including male sex workers (MSW). Our study aimed to assess mpox knowledge and attitude towards mpox vaccination among MSW in China. Methods: A web-based, cross-sectional survey was conducted in August 2022. We collected participants’ socio-demographic characteristics and knowledge with 15 knowledge items related to mpox. Modified Bloom’s cut-off points of 80% (total score > 12) was used to indicate good knowledge. Multivariable regression analysis was used to assess factors of mpox knowledge and attitude towards mpox vaccination. Results: A total of 154 MSW were recruited (age: median = 22, interquartile range, IQR = 12). Of the 154 MSW, 49.4% had good knowledge of mpox, and 63.0% were willing to be vaccinated against mpox. We found that good knowledge was associated with being single [adjusted odds ratio (AOR) = 2.46, 95% confident interval (CI) (1.22–4.87)], being unemployed [5.01, 1.21–20.70] and willingness to be vaccinated [2.51, 1.14–5.54]. Willingness to get vaccinated was related to age [1.06, 1.00–1.12], chronic diseases history [8.53, 1.01–71.68], and agreement with “priority for high-risk groups if mpox vaccine is in short supply” [2.57, 1.01–6.54]. Conclusions: We found that MSW had suboptimal mpox knowledge and a high willingness to be vaccinated against mpox. MSW who are single and willing to be vaccinated may have good knowledge of mpox. These findings underscore the necessity of providing health education on mpox among MSW. When the mpox vaccine is in short supply, priority should be given to high-risk groups, such as MSW.
The Combination of an mRNA Immunogen, a TLR7 Agonist and a PD1 Blocking Agent Enhances In-Vitro HIV T-Cell Immune Responses
Authors: Usero Lorena , Leal Lorna , Gómez Carmen Elena , Miralles Laia , Aurrecoechea Elena , Esteban Ignasi , Torres Berta , Inciarte Alexy , Perdiguero Beatriz , Esteban Mariano , García Felipe , Plana Montserrat
Published: January 2023

The development of new strategies to achieve a functional cure for HIV remains a priority. We tested a novel HIV therapeutic vaccine using unmodified mRNA (TMEP-B) and mRNA modified by 1-methyl-3′-pseudouridylyl (TMEP-Bmod) expressing both a multiepitopic sequences from Gag, Pol, and Nef proteins, including different CD4 and CD8 T-cell epitopes functionally associated with HIV control in transfected monocyte-derived dendritic cells (MDDCs) obtained from HIV infected patients. In vitro assays were used to test the mRNAs alone and in combination with immunomodulator agents, such as the TLR-7 agonist Vesatolimod and the PD-1 antagonist Nivolumab to try to improve HIV-specific cellular immune responses. Combining the mRNAs with the immunomodulators enhanced HIV-specific T-cell responses, together with the secretion of IFNγ, IP10, MIP-1α, and MIP-1β, which are fundamental mediators of viral control. Our data suggest that the mRNA vaccine prototypes TMEP-B and TMEP-Bmod, when combined with Vesatolimod and/or Nivolumab, could achieve functional cure for patients with HIV.
Evaluation of the Effectiveness of the Policy of Holding the Second Dose of Vaccination: Lessons from the Outbreak in Ho Chi Minh City
Authors: Trang Vu Thi Thu , Van Truong Le , Van Dat Truong , Elsheikh Randa , Anh Nguyen Tuan , Thang Dang Xuan , Thang Vo Viet , Makram Abdelrahman M. , Huy Nguyen Tien ,   Nagasaki University Collaborative
Published: January 2023

The coronavirus disease 2019 (COVID-19) pandemic has caused a lot of ethical controversy in the equal provision of healthcare, including vaccination. Therefore, our study was designed to assess the impact of Ho Chi Minh City’s policy to hold the second dose of the COVID-19 vaccine. Using a cross-sectional study design to assess low saturation of peripheral oxygen (SPO2) risk based on vaccination status, we included patients who were confirmed to have SARS-CoV-2 and were treated at home. The stepwise method was used to determine participants’ low SPO2 risk-related factors. The average age of the 2836 respondents was 46.43 ± 17.33 (years). Research results have shown that seven factors are related to the low SPO2 status of participants, including age, sneezing, shortness of breath, coughing, and fainting as COVID-19 symptoms, the number of people living with COVID-19, and a history of lung disease. A statistically significant (p = 0.032) finding in this study was that fully vaccinated patients had a 6% lower risk of low SPO2 compared to the first dose less than 21 days group. This result was similar in the vaccine holder group (p < 0.001). Holding the second dose of the COVID-19 vaccine is associated with a lower SPO2 risk than that of fully vaccinated patients. Therefore, this approach should be considered by governments as it could bring a greater benefit to the community.
Healthcare Provider’s Perceived Self-Efficacy in HPV Vaccination Hesitancy Counseling and HPV Vaccination Acceptance
Authors: Osaghae Ikponmwosa , Darkoh Charles , Chido-Amajuoyi Onyema Greg , Chan Wenyaw , Padgett Wermuth Paige , Pande Mala , Cunningham Sonia A. , Shete Sanjay
Published: January 2023

Background: HPV vaccine hesitancy is a key contributor to the sub-optimal HPV vaccination uptake in the United States. We aimed to determine the association between healthcare providers’ self-efficacy in HPV vaccination hesitancy counseling and HPV vaccination acceptance after initial and follow-up counseling sessions. Methods: Population-based cross-sectional study of healthcare providers (HCPs) practicing in Texas. Logistic regression analyses were used to determine the odds of HPV vaccination acceptance by vaccine-hesitant patients. Additionally, generalized estimating equations were used to compare HPV vaccination acceptance by hesitant patients after follow-up versus initial counseling sessions. Results: 1283 HCPs completed the survey with a mean (SD) age of 47.1 (11.3) years. HCPs who believed that they were very/completely confident in counseling HPV-vaccine-hesitant parents had higher odds of observing HPV vaccination acceptance very often/always after an initial counseling session (adjusted odds ratio (AOR): 3.50; 95% CI: 2.25–5.44) and after follow-up counseling sessions (AOR: 2.58; 95% CI: 1.66–4.00) compared to HCPs that perceived they were not at all/somewhat/moderately confident. The odds of HPV vaccination being accepted very often/always by vaccine-hesitant parents was 61% (AOR: 1.61; 95% CI: 1.32–1.95) higher after follow-up counseling sessions compared to an initial counseling session. The results were similar for the counseling of HPV-vaccine-hesitant adult patients. Conclusions: The confidence level of HCPs in counseling hesitant parents and adult patients impacts HPV vaccination acceptance. Importantly, acceptance was higher after follow-up counseling sessions than initial counseling sessions. HCPs should receive training in HPV vaccination counseling to enhance their confidence in counseling hesitant patients and should utilize every visit to counsel hesitant patients.
Immunoinformatics Approach to Design a Multi-Epitope Nanovaccine against Leishmania Parasite: Elicitation of Cellular Immune Responses
Authors: Margaroni Maritsa , Agallou Maria , Tsanaktsidou Evgenia , Kammona Olga , Kiparissides Costas , Karagouni Evdokia
Published: January 2023

Leishmaniasis is a vector-borne disease caused by an intracellular parasite of the genus Leishmania with different clinical manifestations that affect millions of people worldwide, while the visceral form may be fatal if left untreated. Since the available chemotherapeutic agents are not satisfactory, vaccination emerges as the most promising strategy for confronting leishmaniasis. In the present study, a reverse vaccinology approach was adopted to design a pipeline starting from proteome analysis of three different Leishmania species and ending with the selection of a pool of MHCI- and MHCII-binding epitopes. Epitopes from five parasite proteins were retrieved and fused to construct a multi-epitope chimeric protein, named LeishChim. Immunoinformatics analyses indicated that LeishChim was a stable, non-allergenic and immunogenic protein that could bind strongly onto MHCI and MHCII molecules, suggesting it as a potentially safe and effective vaccine candidate. Preclinical evaluation validated the in silico prediction, since the LeishChim protein, encapsulated simultaneously with monophosphoryl lipid A (MPLA) into poly(D,L-lactide-co-glycolide) (PLGA) nanoparticles, elicited specific cellular immune responses when administered to BALB/c mice. These were characterized by the development of memory CD4+ T cells, as well as IFNγ- and TNFα-producing CD4+ and CD8+ T cells, supporting the potential of LeishChim as a vaccine candidate.
Quasispecies Nature of RNA Viruses: Lessons from the Past
Authors: Singh Kiran , Mehta Deepa , Dumka Shaurya , Chauhan Aditya Singh , Kumar Sachin
Published: January 2023

Viral quasispecies are distinct but closely related mutants formed by the disparity in viral genomes due to recombination, mutations, competition, and selection pressure. Theoretical derivation for the origin of a quasispecies is owed to the error-prone replication by polymerase and mutants of RNA replicators. Here, we briefly addressed the theoretical and mathematical origin of quasispecies and their dynamics. The impact of quasispecies for major salient human pathogens is reviewed. In the current global scenario, rapid changes in geographical landscapes favor the origin and selection of mutants. It comes as no surprise that a cauldron of mutants poses a significant risk to public health, capable of causing pandemics. Mutation rates in RNA viruses are magnitudes higher than in DNA organisms, explaining their enhanced virulence and evolvability. RNA viruses cause the most devastating pandemics; for example, members of the Orthomyxoviridae family caused the great influenza pandemic (1918 flu or Spanish flu), the SARS (severe acute respiratory syndrome) and MERS (Middle East respiratory syndrome) outbreak, and the human immunodeficiency viruses (HIV), lentiviruses of the Retroviridae family, caused worldwide devastation. Rapidly evolving RNA virus populations are a daunting challenge for the designing of effective control measures like vaccines. Developing awareness of the evolutionary dispositions of RNA viral mutant spectra and what influences their adaptation and virulence will help curtail outbreaks of past and future pathogens.
Performance and Tolerance of a Protocol for Idiopathic Chronic Greasy Seborrhea in 18 Dogs Using a Shampoo and Mousse Containing Plant Extracts
Authors: Kondratjeva Jevgenija , Brun Jessie , Amalric Nicolas , Moog Fabien , Combarros Daniel , Pressanti Charline , Zemirline Claudine , Maubert Nadège , Ollivier Elodie , Gatellet Marina , Cadiergues Marie Christine
Published: January 2023

The study aimed to evaluate the tolerance, performance and effect on hair lipids and skin hydration of a protocol combining applications of one shampoo and subsequent mousses containing plant extracts (Ophytrium and Seboliance) in dogs with an undiagnosed chronic greasy keratinisation disorder. Six dogs were washed with plain water on day (D)0. Twelve dogs were shampooed on D0 and received eight mousse applications at 48–72 h intervals from D2 to D18. Clinical score (CS), Natural Moisturizing Factors (NMF) and hair lipids (HL) were evaluated on D0, D0 + 4 h, D7, D14 and D24. At baseline, no significant differences were observed in CS, NMF and HL between groups. In the control group, CS and HL remained stable throughout the study while a slight decrease in NMF was observed at D0 + 4 h. CS was significantly reduced in the test group between D0 and D7 (−53%) which reached 91% at D24 (p < 0.05), with no side effects. NMF levels decreased in the test group at D0 + 4 h (−73%, p < 0.0001) and returned to baseline from D14. In conclusion, one shampoo and subsequent mousse applications rapidly and safely improved coat quality in dogs with an undiagnosed keratinisation disorder without affecting NMF and HL contents over the study period.
Cybersickness in Virtual Reality Questionnaire (CSQ-VR): A Validation and Comparison against SSQ and VRSQ
Authors: Kourtesis Panagiotis , Linnell Josie , Amir Rayaan , Argelaguet Ferran , MacPherson Sarah E.
Published: January 2023

Cybersickness is a drawback of virtual reality (VR), which also affects the cognitive and motor skills of users. The Simulator Sickness Questionnaire (SSQ) and its variant, the Virtual Reality Sickness Questionnaire (VRSQ), are two tools that measure cybersickness. However, both tools suffer from important limitations which raise concerns about their suitability. Two versions of the Cybersickness in VR Questionnaire (CSQ-VR), a paper-and-pencil and a 3D–VR version, were developed. The validation of the CSQ-VR and a comparison against the SSQ and the VRSQ were performed. Thirty-nine participants were exposed to three rides with linear and angular accelerations in VR. Assessments of cognitive and psychomotor skills were performed at baseline and after each ride. The validity of both versions of the CSQ-VR was confirmed. Notably, CSQ-VR demonstrated substantially better internal consistency than both SSQ and VRSQ. Additionally, CSQ-VR scores had significantly better psychometric properties in detecting a temporary decline in performance due to cybersickness. Pupil size was a significant predictor of cybersickness intensity. In conclusion, the CSQ-VR is a valid assessment of cybersickness with superior psychometric properties to SSQ and VRSQ. The CSQ-VR enables the assessment of cybersickness during VR exposure, and it benefits from examining pupil size, a biomarker of cybersickness.
Comparative Study on Carbon Emission of the Cyanobacteria Mud Disposal Process
Authors: Wang Liying , Li Youcai , Zhang Qingbo
Published: January 2023

Endogenous pollutants such as cyanobacteria have an essential impact on the global carbon cycle and climate. Finding a reasonable way to dispose of them has become an urgent task for current watershed management and ecological restoration. According to the engineering practice of cyanobacteria treatment by aerobic fermentation, the carbon emissions of three typical cyanobacterial resource utilization processes, aerobic fermentation without auxiliary materials, aerobic fermentation with auxiliary materials, and incineration for power generation, are compared in this paper, using the mandatory guidelines by the Intergovernmental Panel on Climate Change (IPCC). The results show that the treatment of cyanobacterial mud through aerobic fermentation without auxiliary materials can realize the goal of the harmless recycling of cyanobacterial resources with less carbon emissions, at 175.3 kg CO2·t−1. In addition, each link’s impact on the overall carbon emission process was analyzed. In aerobic fermentation with auxiliary materials, the carbon emissions were significantly contributed by the auxiliary materials, which was accounted for 46.3% of the carbon emission of the whole process and 32.77% of the drying-incineration process. In contrast, with the lowest carbon emission level, aerobic fermentation without auxiliary materials can avoid the production of carbon emissions caused by auxiliary fermentation materials.
Research on Longitudinal Control Algorithm of Adaptive Cruise Control System for Pure Electric Vehicles
Authors: Chu Liang , Li Huichao , Xu Yanwu , Zhao Di , Sun Chengwei
Published: January 2023

The vehicle longitudinal control algorithm is the core function of the adaptive cruise control system, whose main task is to convert vehicle acceleration and deceleration requirements into vehicle driving and braking commands so that the vehicle can quickly and accurately track the desired acceleration. Traditional longitudinal control algorithms rely on accurate vehicle dynamic modeling or complex controller parameter calibrations. To overcome those difficulties, a longitudinal control algorithm based on RBF-PID is proposed in this paper. The algorithm uses the RBFNN (radial basis function neural network), which can simply and quickly approximate any complex nonlinear system, to identify the Jacobian information of the vehicle and perform parameter tuning for PID control and achieve vehicle longitudinal control with self-tuning capability. Finally, the algorithm of this paper is verified by the joint simulation of Matlab/Simulink and Carsim. The results show that this algorithm has a better response rate and anti-jamming capability than the traditional PID control and can achieve accurate and rapid tracking of the desired acceleration.