bluuebunny/crossref_metadata_2025 huggingface dataset:
Status of the Resistance of Aphis gossypii Glover, 1877 (Hemiptera: Aphididae) to Afidopyropen Originating from Microbial Secondary Metabolites in China
Authors: Li Ren , Cheng Shenhang , Liang Pingzhuo , Chen Zhibin , Zhang Yujia , Liang Pei , Zhang Lei , Gao Xiwu
Published: November 2022

The resistance of cotton aphids to various forms of commonly used pesticides has seriously threatened the safety of the cotton production. Afidopyropen is a derivative of microbial metabolites with pyropene insecticide, which has been shown to be effective in the management of Aphis gossypii. Several field populations of Aphis gossypii were collected from the major cotton-producing regions of China from 2019 to 2021. The resistance of these populations to afidopyropen was estimated using the leaf-dipping method. The LC50 values of these field populations ranged from 0.005 to 0.591 mg a.i. L−1 in 2019, from 0.174 to 4.963 mg a.i. L−1 in 2020 and from 0.517 to 14.16 mg a.i. L−1 in 2021. The resistance ratios for all A. gossypii populations ranged from 0.03 to 3.97 in 2019, from 1.17 to 33.3 in 2020 and from 3.47 to 95.06 in 2021. The afidopyropen resistance exhibited an increasing trend in the field populations of Cangzhou, Binzhou, Yuncheng, Kuerle, Kuitun, Changji and Shawan from 2019 to 2021. This suggests that the resistance development of the cotton aphid to afidopyropen is inevitable. Therefore, it is necessary to rotate or mix afidopyropen with other insecticides in order to inhibit the development of afidopyropen resistance in field populations.
Neurophysiological Basis of Deep Brain Stimulation and Botulinum Neurotoxin Injection for Treating Oromandibular Dystonia
Authors: Maezawa Hitoshi , Hirata Masayuki , Yoshida Kazuya
Published: November 2022

Oromandibular dystonia (OMD) induces severe motor impairments, such as masticatory disturbances, dysphagia, and dysarthria, resulting in a serious decline in quality of life. Non-invasive brain-imaging techniques such as electroencephalography (EEG) and magnetoencephalography (MEG) are powerful approaches that can elucidate human cortical activity with high temporal resolution. Previous studies with EEG and MEG have revealed that movements in the stomatognathic system are regulated by the bilateral central cortex. Recently, in addition to the standard therapy of botulinum neurotoxin (BoNT) injection into the affected muscles, bilateral deep brain stimulation (DBS) has been applied for the treatment of OMD. However, some patients’ OMD symptoms do not improve sufficiently after DBS, and they require additional BoNT therapy. In this review, we provide an overview of the unique central spatiotemporal processing mechanisms in these regions in the bilateral cortex using EEG and MEG, as they relate to the sensorimotor functions of the stomatognathic system. Increased knowledge regarding the neurophysiological underpinnings of the stomatognathic system will improve our understanding of OMD and other movement disorders, as well as aid the development of potential novel approaches such as combination treatment with BoNT injection and DBS or non-invasive cortical current stimulation therapies.
Correction: Srisuphanunt et al. Prognostic Indicators for the Early Prediction of Severe Dengue Infection: A Retrospective Study in a University Hospital in Thailand. Trop. Med. Infect. Dis. 2022, 7, 162
Authors: Srisuphanunt Mayuna , Puttaruk Palakorn , Kooltheat Nateelak , Katzenmeier Gerd , Wilairatana Polrat
Published: November 2022

In the original publication [...]
Effect of Oral Antidiabetic Drugs on Tuberculosis Risk and Treatment Outcomes: Systematic Review and Meta-Analysis
Authors: Meregildo-Rodriguez Edinson Dante , Asmat-Rubio Martha Genara , Zavaleta-Alaya Petterson , Vásquez-Tirado Gustavo Adolfo
Published: November 2022

Tuberculosis and diabetes mellitus are two global pandemics and rising public health problems. Recent studies suggest that oral antidiabetic drugs (OADs) could reduce the risk of tuberculosis and improve clinical outcomes. However, the evidence is controversial. Therefore, we aimed to assess the effect of OADs on the risk of tuberculosis and treatment outcomes. We systematically searched for six databases from inception to 31 August 2022. We followed a predefined PICO/PECO strategy and included two randomized controlled trials and sixteen observational studies. This study collects 1,109,660 participants, 908,211 diabetic patients, and at least 13,841 tuberculosis cases. Our results show that metformin decreases the risk of active tuberculosis by 40% (RR 0.60; 95% CI 0.47–0.77) in diabetic patients. In addition, metformin exhibits a dose-response gradient (medium doses reduce the risk of active tuberculosis by 45%, while high doses reduce this risk by 52%). On the other hand, DPP IV inhibitors increase the risk of active tuberculosis by 43% (RR 1.43; 95% CI 1.02–2.02). Subgroup analysis showed that study design and metformin dose accounted for the heterogeneity. We conclude that metformin significantly protects against active tuberculosis among diabetic patients. On the contrary, DPP IV inhibitors could increase the risk of developing active tuberculosis.
Malaria in Senegal: Recent and Future Changes Based on Bias-Corrected CMIP6 Simulations
Authors: Diouf Ibrahima , Ndione Jacques-André , Gaye Amadou Thierno
Published: November 2022

Malaria is a constant reminder of the climate change impacts on health. Many studies have investigated the influence of climatic parameters on aspects of malaria transmission. Climate conditions can modulate malaria transmission through increased temperature, which reduces the duration of the parasite’s reproductive cycle inside the mosquito. The rainfall intensity and frequency modulate the mosquito population’s development intensity. In this study, the Liverpool Malaria Model (LMM) was used to simulate the spatiotemporal variation of malaria incidence in Senegal. The simulations were based on the WATCH Forcing Data applied to ERA-Interim data (WFDEI) used as a point of reference, and the biased-corrected CMIP6 model data, separating historical simulations and future projections for three Shared Socio-economic Pathways scenarios (SSP126, SSP245, and SSP585). Our results highlight a strong increase in temperatures, especially within eastern Senegal under the SSP245 but more notably for the SSP585 scenario. The ability of the LMM model to simulate the seasonality of malaria incidence was assessed for the historical simulations. The model revealed a period of high malaria transmission between September and November with a maximum reached in October, and malaria results for historical and future trends revealed how malaria transmission will change. Results indicate a decrease in malaria incidence in certain regions of the country for the far future and the extreme scenario. This study is important for the planning, prioritization, and implementation of malaria control activities in Senegal.
Tidal Deformability of Neutron Stars in Unimodular Gravity
Authors: Yang Rui-Xin , Xie Fei , Liu Dao-Jun
Published: November 2022

Unimodular gravity is a modified theory with respect to general relativity by an extra condition that the determinant of the metric is fixed. Especially, if the energy-momentum tensor is not imposed to be conserved separately, a new geometric structure will appear with potential observational signatures. In this paper, we study the tidal deformability of a compact star in unimodular gravity under the assumption of a non-conserved energy-momentum tensor. Both the electric-type and magnetic-type quadrupole tidal Love numbers are calculated for neutron stars using the polytrope model. It is found that the electric-type tidal Love numbers are monotonically increasing, but the magnetic-type ones are decreasing, with the increase in the non-conservation parameter. Compared with the observational data from the detected gravitational-wave events, a small negative non-conservation parameter is favored.
Use of Human Lung Tissue Models for Screening of Drugs against SARS-CoV-2 Infection
Authors: McAuley Alexander J. , Jansen van Vuren Petrus , Mohammed Muzaffar-Ur-Rehman , Faheem  , Goldie Sarah , Riddell Shane , Gödde Nathan J. , Styles Ian K. , Bruce Matthew P. , Chahal Simran , Keating Stephanie , Blasdell Kim R. , Tachedjian Mary , O’Brien Carmel M. , Singanallur Nagendrakumar Balasubramanian , Viana John Noel , Vashi Aditya V. , Kirkpatrick Carl M. , MacRaild Christopher A. , Shah Rohan M. , Vincan Elizabeth , Athan Eugene , Creek Darren J. , Trevaskis Natalie L. , Murugesan Sankaranarayanan , Kumar Anupama , Vasan Seshadri S.
Published: November 2022

The repurposing of licenced drugs for use against COVID-19 is one of the most rapid ways to develop new and alternative therapeutic options to manage the ongoing pandemic. Given circa 7817 licenced compounds available from Compounds Australia that can be screened, this paper demonstrates the utility of commercially available ex vivo/3D airway and alveolar tissue models. These models are a closer representation of in vivo studies than in vitro models, but retain the benefits of rapid in vitro screening for drug efficacy. We demonstrate that several existing drugs appear to show anti-SARS-CoV-2 activity against both SARS-CoV-2 Delta and Omicron Variants of Concern in the airway model. In particular, fluvoxamine, as well as aprepitant, everolimus, and sirolimus, has virus reduction efficacy comparable to the current standard of care (remdesivir, molnupiravir, nirmatrelvir). Whilst these results are encouraging, further testing and efficacy studies are required before clinical use can be considered.
Molecular Characterization and Phylogenetic Analysis of Feline Calicivirus Isolated in Guangdong Province, China from 2018 to 2022
Authors: Mao Jianwei , Ye Shaotang , Li Qi , Bai Yumeizi , Wu Jieyan , Xu Liang , Wang Zhen , Wang Jingyu , Zhou Pei , Li Shoujun
Published: November 2022

Feline calicivirus (FCV) is a common feline infectious pathogen that mainly causes upper respiratory tract disease. To investigate the prevalence of FCV in Guangdong Province in China, a total of 152 nasal and throat swabs from cats suspected of FCV infection were collected in veterinary clinics or shelters from 2018 to 2022. The positive detection rate of FCV was 28.9% (44/152) by RT-PCR. In addition, twenty FCV isolates were successfully isolated and purified. Eleven out of twenty isolates were selected for further phylogenetic analyses based on the capsid protein VP1; our results revealed that seven isolates were in genogroup I, and four were in genogroup II. Notably, according to the whole genome phylogenetic tree, FCV-SCAU-11 was in the same branch as Korean isolates, and recombination analysis revealed that the FCV-SCAU-11 isolate showed potential recombinant events between the FCV-SH isolate and FCV-GXNN03-20 isolate. Furthermore, the virus replication kinetics indicated that FCV-SCAU-10, with clinically severe symptoms in patient cats, performed a more efficient replication in vitro. In conclusion, this study revealed the genetic diversity of FCVs in Guangdong Province, providing a reference for novel vaccine candidate strains and the development of effective strategies for preventing FCV infection in cats.
Cytomegalovirus Specific Serological and Molecular Markers in a Series of Pregnant Women with Cytomegalovirus Non Primary Infection
Authors: Périllaud-Dubois Claire , Letamendia Emmanuelle , Bouthry Elise , Rafek Rana , Thouard Isabelle , Vieux-Combe Corinne , Picone Olivier , Cordier Anne-Gaël , Vauloup-Fellous Christelle
Published: November 2022

(1) Background: In a period where systematic screening of CMV during pregnancy is still debated, diagnosis of non primary infection (NPI) remains challenging and an obstacle to systematic screening. Our aim is to report kinetics of serological and molecular CMV markers of NPI. (2) Methods: We identified immunocompetent pregnant women with CMV NPI as women known to be seropositive for CMV before pregnancy who gave birth to cCMV infected infants. We performed CMV-IgG, CMV-IgM, CMV-IgG avidity and CMV PCR retrospectively on sequential serum samples collected during pregnancy. (3) Results: We collected 195 serum samples from 53 pregnant women with NPI during pregnancy. For 29/53 (55%) patients, no markers of active infection were observed (stable IgG titers, negative IgM and negative PCR). CMV PCR was positive in at least one serum for 18/53 (34%) patients and median viral load was 46 copies/mL, IQR (21–65). (4) Conclusions: For more than half of patients with confirmed CMV NPI during pregnancy, available diagnostic tools are liable to fail in detecting an active infection. These should therefore not be used and universal neonatal screening for CMV remains the only way to detect all cCMV infections.
Inter-Fighting between Influenza A Virus NS1 and β-TrCP: A Novel Mechanism of Anti-Influenza Virus
Authors: Sun Haiwei , Wang Kai , Yao Wei , Liu Jingyi , Lv Lu , Shi Xinjin , Chen Hongjun
Published: November 2022

Influenza A virus (IAV) prevents innate immune signaling during infection. In our previous study, the production of pro-inflammatory cytokines was associated with Cullin-1 RING ligase (CRL1), which was related to NF-κB activation. However, the underlying mechanism is unclear. Here, an E3 ligase, β-transducin repeat-containing protein (β-TrCP), was significantly downregulated during IAV infection. Co-IP analysis revealed that non-structural 1 protein (NS1) interacts with β-TrCP. With co-transfection, an increase in NS1 expression led to a reduction in β-TrCP expression, affecting the level of IκBα and then resulting in repression of the activation of the NF-κB pathway during IAV infection. In addition, β-TrCP targets the viral NS1 protein and significantly reduces the replication level of influenza virus. Our results provide a novel mechanism for influenza to modulate its immune response during infection, and β-TrCP may be a novel target for influenza virus antagonism.
Global Transcriptome Analyses of Cellular and Viral mRNAs during HAdV-C5 Infection Highlight New Aspects of Viral mRNA Biogenesis and Cytoplasmic Viral mRNA Accumulations
Authors: Alemán Margarita Valdés , Bertzbach Luca D. , Speiseder Thomas , Ip Wing Hang , González Ramón A. , Dobner Thomas
Published: November 2022

It is well established that human adenoviruses such as species C, types 2 and 5 (HAdV-C2 and HAdV-C5), induce a nearly complete shutoff of host-cell protein synthesis in the infected cell, simultaneously directing very efficient production of viral proteins. Such preferential expression of viral over cellular genes is thought to be controlled by selective nucleocytoplasmic export and translation of viral mRNA. While detailed knowledge of the regulatory mechanisms responsible for the translation of viral mRNA is available, the viral or cellular mechanisms of mRNA biogenesis are not completely understood. To identify parameters that control the differential export of viral and cellular mRNAs, we performed global transcriptome analyses (RNAseq) and monitored temporal nucleocytoplasmic partitioning of viral and cellular mRNAs during HAdV-C5 infection of A549 cells. Our analyses confirmed previously reported features of the viral mRNA expression program, as a clear shift in viral early to late mRNA accumulation was observed upon transition from the early to the late phase of viral replication. The progression into the late phase of infection, however, did not result in abrogation of cellular mRNA export; rather, viral late mRNAs outnumbered viral early and most cellular mRNAs by several orders of magnitude during the late phase, revealing that viral late mRNAs are not selectively exported but outcompete cellular mRNA biogenesis.
An Optimized Bioassay for Screening Combined Anticoronaviral Compounds for Efficacy against Feline Infectious Peritonitis Virus with Pharmacokinetic Analyses of GS-441524, Remdesivir, and Molnupiravir in Cats
Authors: Cook Sarah , Wittenburg Luke , Yan Victoria C. , Theil Jacob H. , Castillo Diego , Reagan Krystle L. , Williams Sonyia , Pham Cong-Dat , Li Chun , Muller Florian L. , Murphy Brian G.
Published: November 2022

Feline infectious peritonitis (FIP) is a fatal disease of cats that currently lacks licensed and affordable vaccines or antiviral therapeutics. The disease has a spectrum of clinical presentations including an effusive (“wet”) form and non-effusive (“dry”) form, both of which may be complicated by neurologic or ocular involvement. The feline coronavirus (FCoV) biotype, termed feline infectious peritonitis virus (FIPV), is the etiologic agent of FIP. The objective of this study was to determine and compare the in vitro antiviral efficacies of the viral protease inhibitors GC376 and nirmatrelvir and the nucleoside analogs remdesivir (RDV), GS-441524, molnupiravir (MPV; EIDD-2801), and β-D-N4-hydroxycytidine (NHC; EIDD-1931). These antiviral agents were functionally evaluated using an optimized in vitro bioassay system. Antivirals were assessed as monotherapies against FIPV serotypes I and II and as combined anticoronaviral therapies (CACT) against FIPV serotype II, which provided evidence for synergy for selected combinations. We also determined the pharmacokinetic properties of MPV, GS-441524, and RDV after oral administration to cats in vivo as well as after intravenous administration of RDV. We established that orally administered MPV at 10 mg/kg, GS-441524 and RDV at 25 mg/kg, and intravenously administered RDV at 7 mg/kg achieves plasma levels greater than the established corresponding EC50 values, which are sustained over 24 h for GS-441514 and RDV.
Association of Human Leucocyte Antigen Polymorphism with Coronavirus Disease 19 in Renal Transplant Recipients
Authors: Prasad Narayan , Yadav Brijesh , Prakash Swayam , Yadav Deependra , Singh Ankita , Gautam Sonam , Bhadauria Dharmendra , Kaul Anupama , Patel Manas Ranjan , Behera Manas Ranjan , Kushwaha Ravi Shankar , Yachha Monika
Published: November 2022

Human leucocyte antigens (HLAs) are highly polymorphic glycoproteins expressed at the surface of all nucleated cells. It is required for the SARS-CoV-2 peptide antigen presentation to immune cells for their effector response. However, polymorphism in HLA significantly impacts the binding of SARS-CoV-2 antigenic peptide to the HLA pocket and regulates immune activation. In this study, 514 renal transplant recipients (RTRs) were recruited from the outpatient department and categorized either into symptomatic (n = 173) or asymptomatic groups (n = 341) based on Coronavirus disease-19 (COVID-19) symptoms. The anti-SARS-CoV-2 spike protein-specific IgG antibody titer was measured by chemiluminescent microparticle immune-assay methods in 310 RTRs. The HLA details of 514 patients were retrieved from the electronic medical records and analyzed retrospectively. We found that HLA antigen allele A*24 was significantly associated with asymptomatic infection in 22.78%, HLA C*02 in 4.51%, DRB1*12 in 10.85%, and HLA DQA1*02 in 27.74% of RTRs. Whereas HLA A*29 in 3.46%, A*33 in 26.01%, B*13 in 10.40%, DRB1*10 in 4.62%, DRB1*15 in 39.30%, DRB1*30 in 1.15%, and DQA1*60 in 3.57% of RTRs were associated with symptomatic infection. HLA DRB1*13 and DRB1*15 were associated with moderate to severe degrees of COVID-19 disease. The seroconversion rate in asymptomatic patients was 118/137 (86.13%), had a median titer of 647.80 au/mL, compared to symptomatic patients 148/173 (85.54%) with a median titer of 400.00 au/mL, which was not significant between the two groups (p = 0.88 and 0.13). In conclusion, HLA alleles A*24, C*02, DRB1*12, and DQA1*02 were significantly associated with asymptomatic infection, and A*29, A*33, B*13, DRB1*10, DRB*15, and DRB1*30 were significantly associated with symptomatic infection. HLA DRB1*13 and DRB1*15 were associated with moderate to severe degrees of COVID-19 disease.
Long-Term Effectiveness of Hepatitis B Vaccination in the Protection of Healthcare Students in Highly Developed Countries: A Systematic Review and Meta-Analysis
Authors: Rahmani Alborz , Montecucco Alfredo , Kusznir Vitturi Bruno , Debarbieri Nicoletta , Dini Guglielmo , Durando Paolo
Published: November 2022

Hepatitis B virus represents an important global health problem. In highly developed countries, mass vaccination campaigns of newborns in recent decades have drastically reduced the proportion of carriers. However, workers exposed to blood and body fluids, including healthcare students, can be at risk of exposure. In order to assess the proportion of susceptible individuals in the specific population of healthcare students in highly developed countries, a systematic review and meta-analysis was performed to summarize the evidence on the persistence of humoral immune protection induced by the primary cycle of hepatitis B vaccination, as well as the proportion of true non-responders. Forty-six studies were included in the final analysis (52,749 participants). Overall, the seroprotection prevalence at the pre-exposure assessment was equal to 73.8% (95% CI 69.1–78.0); the prevalence of anamnestic response following the administration of a challenge dose was 90.9% (95% CI 87.7–93.3), demonstrating a high proportion of persistence of vaccination-induced immunity. Among those without evidence of anamnestic response, 5.0% (95% CI 2.1–11.5) were non-responders following the completion of a secondary immunization cycle. These findings demonstrate that the majority of healthcare students vaccinated with the complete HBV primary cycle maintain an effective humoral immunity against this pathogen for over two decades.
Migratory Engineering of T Cells for Cancer Therapy
Authors: Michaelides Stefanos , Obeck Hannah , Kechur Daryna , Endres Stefan , Kobold Sebastian
Published: November 2022

Adoptive cell therapy (ACT) and chimeric antigen receptor (CAR) T cell therapy in particular represents an adaptive, yet versatile strategy for cancer treatment. Convincing results in the treatment of hematological malignancies have led to FDA approval for several CAR T cell therapies in defined refractory diseases. In contrast, the treatment of solid tumors with adoptively transferred T cells has not demonstrated convincing efficacy in clinical trials. One of the main reasons for ACT failure in solid tumors is poor trafficking or access of transferred T cells to the tumor site. Tumors employ a variety of mechanisms shielding themselves from immune cell infiltrates, often translating to only fractions of transferred T cells reaching the tumor site. To overcome this bottleneck, extensive efforts are being undertaken at engineering T cells to improve ACT access to solid tumors. In this review, we provide an overview of the immune cell infiltrate in human tumors and the mechanisms tumors employ toward immune exclusion. We will discuss ways in which T cells can be engineered to circumvent these barriers. We give an outlook on ongoing clinical trials targeting immune cell migration to improve ACT and its perspective in solid tumors.
Effect of Lockdowns on Hospital Staff in a COVID Center: A Retrospective Observational Study
Authors: Vetrugno Giuseppe , Sanguinetti Maurizio , Murri Rita , Sali Michela , Marchetti Simona , Santangelo Rosaria , Fantoni Massimo , Cingolani Antonella , Scoppettuolo Giancarlo , Di Donato Michele , Grassi Vincenzo M. , Foti Federica , Marchese Luca , De-Giorgio Fabio , Oliva Antonio , Staiti Domenico , De Simone Francesco Maria , Pascucci Domenico , Cascini Fidelia , Pastorino Roberta , Pires Marafon Denise , Cambieri Andrea , Laurenti Patrizia , Boccia Stefania , Ricciardi Walter , Franceschi Francesco ,   on behalf of Gemelli-Against-COVID Group
Published: November 2022

At the onset of the SARS-CoV-2 pandemic, individual and social measures were strengthened through restrictive non-pharmaceutical interventions, labelled with the term “lockdown”. In Italy, there were two lockdowns (9 March 2020–3 May 2020 and 3 November 2020–27 March 2021). As part of preventive measures, healthcare workers and the administrative staff population of Policlinico A. Gemelli underwent nasopharyngeal swab tests from 1 March 2020 to 9 February 2022, a long time interval that includes the two aforementioned lockdowns. The population included 8958 people from 1 March 2020 to 31 December 2020; 8981 people from 1 January 2021 to 31 December 2021; and 8981 people from 1 January 2022 to 9 February 2022. We then analysed pseudo-anonymized data, using a retrospective observational approach to evaluate the impact of the lockdown on the incidence of SARS-CoV-2 infections within the population. Given the 14 day contagious period, the swab positivity rate (SPR) among the staff decreased significantly at the end of the first lockdown, every day prior to 18 May 2020, by 0.093 (p < 0.0001, CI = (−0.138–−0.047)). After the fourteenth day post the end of the first lockdown (18 May 2020), the SPR increased daily at a rate of 0.024 (p < 0.0001, 95% CI = (0.013–0.034)). In addition, the SPR appeared to increase significantly every day prior to 17 November 2020 by 0.024 (p < 0.0001, CI = (0.013–0.034)). After the fourteenth day post the start of the second lockdown (17 November 2020), the SPR decreased daily at a rate of 0.039 (p < 0.0001, 95% CI = (−0.050–−0.027)). These data demonstrate that, in our Institution, the lockdowns helped to both protect healthcare workers and maintain adequate standards of care for COVID and non-COVID patients for the duration of the state of emergency in Italy.
Nanoformulations with Leishmania braziliensis Antigens Triggered Controlled Parasite Burden in Vaccinated Golden Hamster (Mesocricetus auratus) against Visceral Leishmaniasis
Authors: Ottino Jennifer , Leite Jaqueline Costa , Melo-Júnior Otoni Alves , González Marco Antonio Cabrera , de Carvalho Tatiane Furtado , Garcia Giani Martins , Batista Maurício Azevedo , Silveira Patrícia , Cardoso Mariana Santos , Bueno Lilian Lacerda , Fujiwara Ricardo Toshio , Santos Renato Lima , Paes Paulo Ricardo de Oliveira , Silveira-Lemos Denise , Martins-Filho Olindo Assis , Galdino Alexsandro Sobreira , Chávez-Fumagalli Miguel Angel , Dutra Walderez Ornelas , Mosqueira Vanessa Carla Furtado , Giunchetti Rodolfo Cordeiro
Published: November 2022

Leishmaniasis is a widespread vector-borne disease in Brazil, with Leishmania (Leishmania) infantum as the primary etiological agent of visceral leishmaniasis (VL). Dogs are considered the main reservoir of this parasite, whose treatment in Brazil is restricted to the use of veterinary medicines, which do not promote a parasitological cure. Therefore, efficient vaccine development is the best approach to Canine Visceral Leishmaniasis (CVL) control. With this in mind, this study used hamsters (Mesocricetus auratus) as an experimental model in an anti-Leishmania preclinical vaccine trial to evaluate the safety, antigenicity, humoral response, and effects on tissue parasite load. Two novel formulations of nanoparticles made from poly(D, L-lactic) acid (PLA) polymer loading Leishmania braziliensis crude antigen (LB) exhibiting two different particle sizes were utilized: LBPSmG (570 nm) and LBPSmP (388 nm). The results showed that the nanoparticles were safe and harmless to hamsters and were antigenic with the induction in LBSap, LBPSmG, and LBPSmG groups of total anti-Leishmania IgG antibodies 30 days after challenge, which persists 200 days in LBSap and LBPSmP. At the same time, a less pronounced hepatosplenomegaly in LBSap, LBPSmG, and LBPSmP was found when compared to control groups, as well as a less pronounced inflammatory infiltrate and granuloma formation in the spleen. Furthermore, significant reductions of 84%, 81%, and 90% were observed in spleen parasite burden accessed by qPCR in the LBSap, LBPSmG, and LBPSmP groups, respectively. In this way, LBSap, LBPSmG, and LBPSmP formulations showed better results in vaccinated and L. infantum-challenged animals in further reducing parasitic load in the spleen and attenuating lesions in liver and splenic tissues. This results in safe, harmless nanoformulation vaccines with significant immunogenic and infection control potential. In addition, animals vaccinated with LBPSmP had an overall reduction in parasite burden in the spleen, indicating that a smaller nanoparticle could be more efficient in targeting antigen-presenting cells.
Severity and Mortality Predictors of COVID-19 Patients with Thrombotic Events-Evidence from the “COVID-One” Hospital in Albania
Authors: Como Najada , Mechili Enkeleint A. , Qato Migena , Meta Esmeralda , Strakosha Arjana , Fico Albana , Kenga Albana , Patelarou Athina E. , Patelarou Evridiki
Published: November 2022

COVID-19 vaccination leads to lower infection, morbidity, and mortality rates. However, COVID-19 infection leads to the development of coagulopathy-related manifestations in the form of both venous and arterial thromboembolism. This study aimed to assess the severity and mortality predictors of COVID-19 patients with thrombotic events in hospitalized patients in Albania. This is a retrospective study conducted in the “Mother Tereza” University Hospital of Tirana. Data were retrieved from the electronic databases of the hospital and only COVID-19 cases admitted to the infectious department during August–December 2020 were selected. Patients who, at admission, had a C-reactive protein (CRP) (mg/L) more than double and a D-dimer (ng/mL) more than triple according to international standards were included in the study. We performed univariate and multivariable logistic regression analysis, calculating unadjusted and adjusted odds ratios (ORs). A p-value < 0.05 was considered statistically significant. The study population included 60 hospitalized persons with a mean age of 64.4 years. Increased lactate dehydrogenase (LDH) (OR = 2.93; 95% CI = 0.82–10.42, p-value = 0.1) and increased creatine kinase (CK) (OR = 2.17; 95% CI = 0.63–7.46, p-value = 0.22) were related with increased probability of death. Moreover, a decreased number of lymphocytes was associated with increased mortality but with no statistical significance (OR = 0.40; 95% CI = 0.11–1.40, p-value = 0.15). The survival rate was higher for patients without comorbidities (p = 0.045). These results could serve as a baseline and as a reference for healthcare personnel who provides services to hospitalized patients with COVID-19. Further studies should take into consideration the vaccination of the population as well as including more hospitals and patients.
Brazilian Adults’ Attitudes and Practices Regarding the Mandatory COVID-19 Vaccination and Their Hesitancy towards Childhood Vaccination
Authors: Martinez Edson Zangiacomi , Zucoloto Miriane Lucindo , Ramos Vânia Pinheiro , Dutra Carla Daiane Costa , de Jesus Giselle Juliana , Esteves Arinete Véras Fontes , Abreu Isabella Schroeder , Mombelli Monica Augusta , Reis Roberta Alvarenga , Campoamor Marilia Marcondes , da Silva Wanderson Roberto , dos Santos Claudia Benedita
Published: November 2022

Background: This study investigated the attitudes and practices of Brazilian adults regarding the mandatory COVID-19 vaccination and their hesitancy towards the vaccination of children. Methods: Between March and May 2022, Brazilian adults answered an online questionnaire distributed through social media. The SAGE-WG questionnaire was adapted to measure hesitancy to the vaccination of children. Results: Of the 1007 participants, 67.4% believed that adult COVID-19 vaccination should be mandatory. Just over half of the participants (51.5%) believed that parents and/or guardians should decide if their children should be vaccinated against COVID-19 or not and 9.1% were unsure. Individuals who were younger, non-religious and had higher awareness of COVID-19 risks and critics of the federal government’s performance in combating the pandemic were more likely to agree with mandatory adult vaccination. However, less agreement among parents and/or guardians concerning children’s vaccination was observed, with lower scores for hesitancy to the vaccination of children. Conclusion: In Brazil, there is still far from a consensus on mandatory COVID-19 vaccination for adults and a significant proportion of the population believes that parents and/or guardians should be free to decide on their children’s vaccination. These views are associated with age, religion, knowledge of COVID-19 risks and political inclination.
Molecular Lipopolysaccharide Di-Vaccine Protects from Shiga-Toxin Producing Epidemic Strains of Escherichia coli O157:H7 and O104:H4
Authors: Dyatlov Ivan A. , Svetoch Edward A. , Mironenko Anna A. , Eruslanov Boris V. , Firstova Victoria V. , Fursova Nadezhda K. , Kovalchuk Alexander L. , Lvov Vyacheslav L. , Aparin Petr G.
Published: November 2022

Background: Shiga toxin-producing Escherichia coli (STEC) O157:H7 and O104:H4 strains are important causative agents of food-borne diseases such as hemorrhagic colitis and hemolytic–uremic syndrome, which is the leading cause of kidney failure and death in children under 5 years as well as in the elderly. Methods: the native E. coli O157:H7 and O104:H4 lipopolysaccharides (LPS) were partially deacylated under alkaline conditions to obtain apyrogenic S-LPS with domination of tri-acylated lipid A species—Ac3-S-LPS. Results: intraperitoneal immunization of BALB/c mice with Ac3-S-LPS antigens from E. coli O157:H7 and O104:H4 or combination thereof (di-vaccine) at single doses ranging from 25 to 250 µg induced high titers of serum O-specific IgG (mainly IgG1), protected animals against intraperitoneal challenge with lethal doses of homologous STEC strains (60–100% survival rate) and reduced the E. coli O157:H7 and O104:H4 intestinal colonization under an in vivo murine model (6–8-fold for monovalent Ac3-S-LPS and 10-fold for di-vaccine). Conclusions: Di-vaccine induced both systemic and intestinal anti-colonization immunity in mice simultaneously against two highly virulent human STEC strains. The possibility of creating a multivalent STEC vaccine based on safe Ac3-S-LPS seems to be especially promising due to a vast serotype diversity of pathogenic E. coli.
Influenza A(H7N9) Pandemic Preparedness: Assessment of the Breadth of Heterologous Antibody Responses to Emerging Viruses from Multiple Pre-Pandemic Vaccines and Population Immunity
Authors: Levine Min Z. , Holiday Crystal , Bai Yaohui , Zhong Weimin , Liu Feng , Jefferson Stacie , Gross F. Liaini , Tzeng Wen-pin , Fries Louis , Smith Gale , Boutet Philippe , Friel Damien , Innis Bruce L. , Mallett Corey P. , Davis C. Todd , Wentworth David E. , York Ian A. , Stevens James , Katz Jacqueline M. , Tumpey Terrence
Published: November 2022

Influenza A(H7N9) viruses remain as a high pandemic threat. The continued evolution of the A(H7N9) viruses poses major challenges in pandemic preparedness strategies through vaccination. We assessed the breadth of the heterologous neutralizing antibody responses against the 3rd and 5th wave A(H7N9) viruses using the 1st wave vaccine sera from 4 vaccine groups: 1. inactivated vaccine with 2.8 μg hemagglutinin (HA)/dose + AS03A; 2. inactivated vaccine with 5.75 μg HA/dose + AS03A; 3. inactivated vaccine with 11.5 μg HA/dose + MF59; and 4. recombinant virus like particle (VLP) vaccine with 15 μg HA/dose + ISCOMATRIX™. Vaccine group 1 had the highest antibody responses to the vaccine virus and the 3rd/5th wave drifted viruses. Notably, the relative levels of cross-reactivity to the drifted viruses as measured by the antibody GMT ratios to the 5th wave viruses were similar across all 4 vaccine groups. The 1st wave vaccines induced robust responses to the 3rd and Pearl River Delta lineage 5th wave viruses but lower cross-reactivity to the highly pathogenic 5th wave A(H7N9) virus. The population in the United States was largely immunologically naive to the A(H7N9) HA. Seasonal vaccination induced cross-reactive neuraminidase inhibition and binding antibodies to N9, but minimal cross-reactive antibody-dependent cell-mediated cytotoxicity (ADCC) antibodies to A(H7N9).
The Genomic and Genetic Evolution Analysis of Rabbit Astrovirus
Authors: Zhao Qiaoya , Tian Ye , Liu Liping , Jiang Yifei , Sun Haitao , Tan Shanjie , Huang Bing
Published: November 2022

Rabbit astrovirus (RAstV) is a pathogen that causes diarrhea in rabbits, with high infection rate at various stages, which can often cause secondary or mixed infections with other pathogens, bringing great economic losses to the rabbit industry. In this study, 10 samples were collected from cases of rabbits with diarrhea on a rabbit meat farm in the Shandong area of China. The positive sample for astrovirus detected by RT-PCR was inoculated into an RK 13 cell line. A rabbit astrovirus strain named Z317 was successfully isolated, which produced an obvious cytopathic effect 48 h post-inoculation in the RK 13 cell line. The genome structure of this isolate was studied by high-throughput sequencing, showing that the Z317 strain had the highest similarity with the American strain TN/2208/2010, with 92.43% nucleotide homology, belonging to group MRAstV-23. The basic properties of the Z317 capsid (Cap) protein were analyzed, and 10 liner B cell epitopes were screened with the online biosoft Bepipred 2.0 and SVMTriP, including 445–464, 186–205, 655–674, 88–107, 792–811, 45–64, and 257–276 amino acids. This is the first contribution concerning RAstV genomes in China; more studies are needed to understand the diversity and impact of RAstV on rabbit health.
Less Typical Courses of Rhodococcus equi Infections in Foals
Authors: Rakowska Alicja , Marciniak-Karcz Agnieszka , Bereznowski Andrzej , Cywińska Anna , Żychska Monika , Witkowski Lucjan
Published: November 2022

This article aims to present several interesting and less typical courses of Rhodococcus equi infections in foals, collected during the 2019–2021 foaling seasons in some Polish studs. The study was conducted by the Division of Veterinary Epidemiology and Economics, Warsaw University of Life Sciences—SGGW, and concentrated on ultrasonographic contribution to diagnostics and treatment of the disease. Among many standard cases of rhodococcal pneumonia, some rare ones occurred. The aforementioned issues include the potential contribution of rhodococcal infection to a grave outcome in a prematurely born filly, lost as a yearling, so-called “extrapulmonary disorders” (EPD), a hypothesis of inherited immunodeficiency with grave outcome in a breeding dam line from one stud, and macrolide-induced anhidrosis. The main benefit of this report would be to supplement the general picture of clinical rhodococcosis.
Speed-Dependent Eigenmodes for Efficient Simulation of Transverse Rotor Vibration
Authors: Kluger Jocelyn , Crevier Lynn , Udengaard Martin
Published: November 2022

Accurate, computationally efficient simulations enable engineers to design high-performing, cost-efficient, lightweight machines that can leverage models of predictive controls and digital twin predictive maintenance schedules. This study demonstrates a new speed-dependent eigenmode method for accurately and efficiently simulating shaft transverse vibrations. The method involves first independently computing shaft eigenmodes over a range of operating speeds, then correlating the eigenmodes across the different speeds during compilation, and finally adjusting modal properties gradually in accordance with a lookup method during simulation. The new method offers several distinct advantages over the traditional static eigenmodes and Craig-Bampton methods. The new method maintains accuracy over a large range of shaft rotation speeds whereas the static eigenmodes method does not. The new method typically requires fewer modal degrees of freedom than the Craig-Bampton method. Whereas the Craig-Bampton method is limited to modeling changes at the boundaries, the new method is suitable for modeling changing body properties as well as boundary-based changes. For this paper, a fluid-bearing-supported 10 MW direct-drive wind turbine drive shaft is tested virtually in a simulation model developed in Simscape™ Driveline™. Using the simulation statistics, this study compares the accuracy and computational efficiency of the speed-dependent eigenmode method to the traditional finite lumped element, static eigenmode, and Craig–Bampton methods. This paper shows that the new method simulates the chosen system 5 times faster than the traditional lumped mass method and 2.4 times faster than the Craig-Bampton method.
Beyond Seasickness: A Motivated Call for a New Motion Sickness Standard across Motion Environments
Authors: Bos Jelte , Diels Cyriel , Souman Jan
Published: November 2022

Motion sickness is known under several names in different domains, such as seasickness, carsickness, cybersickness, and simulator sickness. As we will argue, these can all be considered manifestations of one common underlying mechanism. In recent years, it has received renewed interest, largely due to the advent of automated vehicles and developments in virtual reality, in particular using head-mounted displays. Currently, the most widely accepted standard to predict motion sickness is ISO 2631-1 (1997), which is based on studies on seasickness and has limited applicability to these newer domains. Therefore, this paper argues for extending the ISO standard to cover all forms of motion sickness, to incorporate factors affecting motion sickness, and to consider various degrees of severity of motion sickness rather than just emesis. This requires a dedicated standard, separate from other effects of whole-body vibration as described in the current ISO 2631-1. To that end, we first provide a sketch of the historical origins of the ISO 2631-1 standard regarding motion sickness and discuss the evidence for a common mechanism underlying various forms of motion sickness. After discussing some methodological issues concerning the measurement of motion sickness, we outline the main knowledge gaps that require further research.
Combining Statistical Clustering with Hydraulic Modeling for Resilient Reduction of Water Losses in Water Distribution Networks: Large Scale Application Study in the City of Patras in Western Greece
Authors: Serafeim Athanasios V. , Kokosalakis George , Deidda Roberto , Fourniotis Nikolaos Th. , Langousis Andreas
Published: November 2022

Partitioning of water distribution networks (WDNs) into pressure management areas (PMAs) or district metered areas (DMAs) is the most widely applied method for the efficient management and reduction of real losses (leakages). Although PMA partitioning is a crucial task, most clustering methods are strongly affected by user-defined weighting factors that heavily affect the final outcome while being associated with heavy computational loads, leading to time-consuming applications. In this work, we use hierarchical clustering enriched with topological proximity constraints to develop an approach for the optimal sizing and allocation of PMAs (or DMAs) in water distribution networks that seeks to minimize water leakages while maintaining a sufficient level of hydraulic resilience. To quantify the latter, we introduce a resilience index that accounts for water leakages and nodal heads in pressure-driven and mixed pressure-demand ways, respectively. The strong points of the introduced approach are that (1) it uses the original pipeline grid as a connectivity matrix in order to avoid unrealistic clustering outcomes; (2) it is statistically rigorous and user unbiased as it is based solely on statistical metrics, thus not relying on and/or being affected by user-defined weighting factors; and (3) it is easy and fast to implement, requiring minimal processing power. The effectiveness of the developed methodology is tested in a large-scale application study in four PMAs (namely Boud, Kentro, Panahaiki, and Prosfygika) of the city of Patras in western Greece, which cover the entire city center and the most important part of the urban fabric of Patras, consisting of approximately 202 km of pipeline and serving approximately 58,000 consumers. Due to its simplicity, minimal computational requirements, and objective selection criteria, the suggested clustering approach for WDN partitioning can serve as an important step toward developing useful decision-making frameworks for water experts and officials, allowing for improved management and reduction of real water losses.
Novel WDR62 and MTR Variants in a Patient With Autosomal Recessive Primary Microcephaly-2 With Polymicrogyria and Homocystinuria-Megaloblastic Anemia
Authors: Dianat Tahereh , Kordi Tamandani Dor Mohammad , Najafi Maryam , Khajeh Ali
Published: November 2022

Background: Autosomal recessive primary microcephaly-2 (MCPH2) is a rare genetic disorder with clinical and genetic heterogeneity. This study aimed to perform high-throughput whole-exome sequencing (WES) to facilitate the diagnosis of the genetic variants responsible for MCPH2 and the comorbidities. Materials and Methods: The WES was performed for a 3-year-old boy with primary microcephaly-2 and homocystinuria-megaloblastic anemia in a consanguineous family. Sequencing and variant calling was conducted by standard bioinformatics tools. Filtering was performed to prioritize novel variants. Finally, the effect of variants on the protein structure and function was assessed using web prediction tools. Results: Using WES, two novel homozygous variants and three novel homozygous variants were identified in the WDR62 and MTR genes as the causes of MCPH2 and homocystinuria-megaloblastic anemia in the affected child, respectively. These frameshift insertion variants are classified as pathogenic and affect the structure and feature of the WDR62 and MTR proteins by changing amino acid sequence and causing nonsense-mediated RNA decay (NMD). Conclusion: Magnetic resonance imaging (MRI) supported polymicrogyria and impaired cerebral cortical development in the affected child. WDR62 as a causative gene plays an essential role in cerebral cortical development, and its pathogenic disease-causing variants are considered as causing factors for MCPH2. Homocystinuria-megaloblastic anemia was a comorbidity associated with microcephaly in this patient, and its variants were confirmed by WES. Overall, performing WES is a necessary and accurate way to rapidly identify the exact causative genetic variants in MCPH2 and the homocystinuria-megaloblastic anemia and manage the disease.
Electrocardiographic and Echocardiographic Findings of Patients With Non-hemorrhagic Stroke
Authors: Mehrabi Farhad , Esmaeeli Omid , Yousefi Hadi , Ezati Rad Roghayeh , Nikparvar Marzieh
Published: November 2022

Background: Stroke is a significant cause of morbidity and mortality worldwide. The association between non-hemorrhagic stroke and some electrocardiographic and echocardiographic findings shows its potential cardiac source. This study aimed to evaluate electrocardiographic and echocardiographic findings of patients with non-hemorrhagic stroke. Methods: This cross-sectional study included 134 patients with non-hemorrhagic stroke admitted to the neurology ward of Shahid Mohammadi hospital, Bandar Abbas, Iran, from 2018 to 2019. Patients’ characteristics including age, gender, family history of stroke, diabetes, hypertension, dyslipidemia, inadequate physical activity, and smoking were recorded. All patients underwent electrocardiography (ECG) and echocardiography. Results: The patients’ mean age was 68.57±12.08 years. Additionally, 84 patients (62.7%) were male. The most common risk factor was dyslipidemia (72.4%) followed by hypertension (64.9%), diabetes (45.5%), smoking (44.8%), and family history of stroke (17.2%). Inadequate physical activity was found in 69.4% of the patients. The most common ECG finding was old myocardial infarction (MI) accounting for 24.6% of the patients, followed by atrial fibrillation (AF) (14.9%) and new MI (3.7%). The most common echocardiographic finding was significant mitral regurgitation (MR) (23.1%), followed by left ventricular systolic dysfunction (21.6%), significant tricuspid regurgitation (TR) (11.2%), mitral stenosis (MS) (4.5%), aortic stenosis (AS) (4.5%), and mitral annulus calcification (MAC) (2.2%). Conclusion: The most common echocardiographic and ECG findings of patients with non-hemorrhagic stroke in this study were MR and old MI and the most common risk factor was dyslipidemia.