bluuebunny/crossref_metadata_2025 huggingface dataset:
Fatty Acid Modification of the Anticancer Peptide LVTX-9 to Enhance Its Cytotoxicity against Malignant Melanoma Cells
Authors: Li Fengjiao , Wu Saizhi , Chen Ninglin , Zhu Jingyu , Zhao Xinxin , Zhang Peng , Zeng Youlin , Liu Zhonghua
Published: December 2021

Spider venom is a valuable resource for the development of novel anticancer drugs. In this study, we focused on novel linear amphipathic α-helical anticancer peptide LVTX-9, which was derived from the cDNA library of the venom gland of the spider Lycosa vittata. The cytotoxicity of LVTX-9 against murine melanoma cells in the range of 1.56–200 μM was tested and found to be significantly lower than those of most anticancer peptides reported. Its IC50 was determined to be 59.2 ± 19.8 μM in a serum or 76.3 ± 12.7 μM in serum-free medium. Fatty acid modification is a promising strategy for improving peptide performance. Therefore, to enhance the cytotoxic activity of LVTX-9, fatty acid modification of this peptide was performed, and five different carbon chain length lipopeptides named LVTX-9-C12-C20 were produced. Among them, the lipopeptide LVTX-9-C18 showed the highest cytotoxic activity in relation to B16-F10 cells, whether in a serum or serum-free medium. Most importantly, the cytotoxic activity of LVTX-9-C18 was improved by about 12.9 times in a serum medium or 19.3 times in a serum-free medium compared to that of LVTX-9. Subsequently, assays including scanning electron microscopy, trypan blue staining, lactate dehydrogenase leakage assay, and hemolytic activity could indicate that the potential direct cell membrane disruption is the main mechanism of LVTX-9-C18 to induce cancer cell death. Furthermore, the LVTX-9-C18 also showed strong cytotoxicity in relation to 3D B16-F10 spheroids, which indicates it might be a promising lead for developing anticancer drugs.
Effect of Botulinum Toxin Injection on the Progression of Hip Dislocation in Patients with Spastic Cerebral Palsy: A Pilot Study
Authors: Lee Yookyung , Lee Seungeun , Jang Joonyoung , Lim Jiwoon , Ryu Ju Seok
Published: December 2021

Hip adductor spasticity is a contributing factor to hip dislocation in patients with cerebral palsy (CP). We hypothesized that botulinum toxin injected into the hip adductor muscles would reduce spasticity and help prevent hip dislocation. Twenty patients with bilateral spastic CP aged 2 to 10 years with gross motor function classification system level IV or V were included. Botulinum toxin was injected into the hip adductor muscles at baseline and at 6-month follow-up. Muscle tone was measured with an eight-channel surface electromyography (EMG) recorder. A hip X-ray was performed, and Reimer’s hip migration index (MI) was measured. The Wilcoxon signed-rank test was used to compare the surface EMG values of the hip muscles at baseline and follow-up. The mean root mean square surface EMG value of the hip adductor muscles was significantly reduced at 1, 2, 3, and 7 months after the first injection, up to approximately 53% of the baseline. The 1-year progression of the hip MI was −0.04%. Repeated sessions of botulinum toxin injections at the hip adductor muscles significantly reduced muscle tone and hip displacement. A botulinum toxin injection may be used as an adjunctive treatment in the prevention of hip dislocation.
Quantum Black Holes and (Re)Solution of the Singularity
Authors: Casadio Roberto
Published: December 2021

Classical general relativity predicts the occurrence of spacetime singularities under very general conditions. Starting from the idea that the spacetime geometry must be described by suitable states in the complete quantum theory of matter and gravity, we shall argue that this scenario cannot be realised physically since no proper quantum state may contain the infinite momentum modes required to resolve the singularity.
Novel Picornavirus Detected in Wild Deer: Identification, Genomic Characterisation, and Prevalence in Australia
Authors: Huaman Jose L. , Pacioni Carlo , Sarker Subir , Doyle Mark , Forsyth David M. , Pople Anthony , Carvalho Teresa G. , Helbig Karla J.
Published: December 2021

The use of high-throughput sequencing has facilitated virus discovery in wild animals and helped determine their potential threat to humans and other animals. We report the complete genome sequence of a novel picornavirus identified by next-generation sequencing in faeces from Australian fallow deer. Genomic analysis revealed that this virus possesses a typical picornavirus-like genomic organisation of 7554 nt with a single open reading frame (ORF) encoding a polyprotein of 2225 amino acids. Based on the amino acid identity comparison and phylogenetic analysis of the P1, 2C, 3CD, and VP1 regions, this novel picornavirus was closely related to but distinct from known bopiviruses detected to date. This finding suggests that deer/bopivirus could belong to a novel species within the genus Bopivirus, tentatively designated as “Bopivirus C”. Epidemiological investigation of 91 deer (71 fallow, 14 sambar and 6 red deer) and 23 cattle faecal samples showed that six fallow deer and one red deer (overall prevalence 7.7%, 95% confidence interval [CI] 3.8–15.0%) tested positive, but deer/bopivirus was undetectable in sambar deer and cattle. In addition, phylogenetic and sequence analyses indicate that the same genotype is circulating in south-eastern Australia. To our knowledge, this study reports for the first time a deer-origin bopivirus and the presence of a member of genus Bopivirus in Australia. Further epidemiological and molecular studies are needed to investigate the geographic distribution and pathogenic potential of this novel Bopivirus species in other domestic and wild animal species.
The Membrane-Anchoring Region of the AcMNPV P74 Protein Is Expendable or Interchangeable with Homologs from Other Species
Authors: Nugnes María Victoria , Targovnik Alexandra Marisa , Mengual-Martí Adrià , Miranda María Victoria , Cerrudo Carolina Susana , Herrero Salvador , Belaich Mariano Nicolás
Published: December 2021

Baculoviruses are insect pathogens that are characterized by assembling the viral dsDNA into two different enveloped virions during an infective cycle: occluded virions (ODVs; immersed in a protein matrix known as occlusion body) and budded virions (BVs). ODVs are responsible for the primary infection in midgut cells of susceptible larvae thanks to the per os infectivity factor (PIF) complex, composed of at least nine essential viral proteins. Among them, P74 is a crucial factor whose activity has been identified as virus-specific. In this work, the p74 gene from AcMNPV was pseudogenized using CRISPR/Cas9 technology and then complemented with wild-type alleles from SeMNPV and HearSNPV species, as well as chimeras combining the P74 amino and carboxyl domains. The results on Spodoptera exigua and Rachiplusia nu larvae showed that an amino terminal sector of P74 (lacking two potential transmembrane regions but possessing a putative nuclear export signal) is sufficient to restore the virus infectivity whether alone or fused to the P74 transmembrane regions of the other evaluated viral species. These results provide novel information about the functional role of P74 and delimit the region on which mutagenesis could be applied to enhance viral activity and, thus, produce better biopesticides.
Time-Resolved Analysis of N-RNA Interactions during RVFV Infection Shows Qualitative and Quantitative Shifts in RNA Encapsidation and Packaging
Authors: Hayashi Miyuki , Schultz Eric P. , Lanchy Jean-Marc , Lodmell J. Stephen
Published: December 2021

Rift Valley fever virus (RVFV) is a negative-sense, tripartite RNA virus that is endemic to Africa and the Arabian Peninsula. It can cause severe disease and mortality in humans and domestic livestock and is a concern for its potential to spread more globally. RVFV’s nucleocapsid protein (N) is an RNA-binding protein that is necessary for viral transcription, replication, and the production of nascent viral particles. We have conducted crosslinking, immunoprecipitation, and sequencing (CLIP-seq) to characterize N interactions with host and viral RNAs during infection. In parallel, to precisely measure intracellular N levels, we employed multiple reaction monitoring mass spectrometry (MRM-MS). Our results show that N binds mostly to host RNAs at early stages of infection, yielding nascent virus particles of reduced infectivity. The expression of N plateaus 10 h post-infection, whereas the intracellular viral RNA concentration continues to increase. Moreover, the virions produced later in infection have higher infectivity. Taken together, the detailed examination of these N–RNA interactions provides insight into how the regulated expression of N and viral RNA produces both infectious and incomplete, noninfectious particles.
The Bank Vole (Clethrionomys glareolus)—Small Animal Model for Hepacivirus Infection
Authors: Röhrs Susanne , Begeman Lineke , Straub Beate K. , Boadella Mariana , Hanke Dennis , Wernike Kerstin , Drewes Stephan , Hoffmann Bernd , Keller Markus , Drexler Jan Felix , Drosten Christian , Höper Dirk , Kuiken Thijs , Ulrich Rainer G. , Beer Martin
Published: December 2021

Many people worldwide suffer from hepatitis C virus (HCV) infection, which is frequently persistent. The lack of efficient vaccines against HCV and the unavailability of or limited compliance with existing antiviral therapies is problematic for health care systems worldwide. Improved small animal models would support further hepacivirus research, including development of vaccines and novel antivirals. The recent discovery of several mammalian hepaciviruses may facilitate such research. In this study, we demonstrated that bank voles (Clethrionomys glareolus) were susceptible to bank vole-associated Hepacivirus F and Hepacivirus J strains, based on the detection of hepaciviral RNA in 52 of 55 experimentally inoculated voles. In contrast, interferon α/β receptor deficient C57/Bl6 mice were resistant to infection with both bank vole hepaciviruses (BvHVs). The highest viral genome loads in infected voles were detected in the liver, and viral RNA was visualized by in situ hybridization in hepatocytes, confirming a marked hepatotropism. Furthermore, liver lesions in infected voles resembled those of HCV infection in humans. In conclusion, infection with both BvHVs in their natural hosts shares striking similarities to HCV infection in humans and may represent promising small animal models for this important human disease.
The Impact of COVID-19 on Mortality in Spain: Monitoring Excess Mortality (MoMo) and the Surveillance of Confirmed COVID-19 Deaths
Authors: León-Gómez Inmaculada , Mazagatos Clara , Delgado-Sanz Concepción , Frías Luz , Vega-Piris Lorena , Rojas-Benedicto Ayelén , Larrauri Amparo
Published: December 2021

Measuring mortality has been a challenge during the COVID-19 pandemic. Here, we compared the results from the Spanish daily mortality surveillance system (MoMo) of excess mortality estimates, using a time series analysis, with those obtained for the confirmed COVID-19 deaths reported to the National Epidemiological Surveillance Network (RENAVE). The excess mortality estimated at the beginning of March 2020 was much greater than what has been observed in previous years, and clustered in a very short time. The cumulated excess mortality increased with age. In the first epidemic wave, the excess mortality estimated by MoMo was 1.5 times higher than the confirmed COVID-19 deaths reported to RENAVE, but both estimates were similar in the following pandemic waves. Estimated excess mortality and confirmed COVID-19 mortality rates were geographically distributed in a very heterogeneous way. The greatest increase in mortality that has taken place in Spain in recent years was detected early by MoMo, coinciding with the spread of the COVID-19 pandemic. MoMo is able to identify risk situations for public health in a timely manner, relying on mortality in general as an indirect indicator of various important public health problems.
Excess Body Mass—A Factor Leading to the Deterioration of COVID-19 and Its Complications—A Narrative Review
Authors: Gryczyńska Weronika , Litvinov Nikita , Bitew Bezawit , Bartosz Zuzanna , Kośmider Weronika , Bogdański Paweł , Skrypnik Damian
Published: December 2021

Currently, the world is facing two serious pandemics: obesity and COVID-19. It is well-established that the prevalence of obesity has risen dramatically, causing a deterioration in the health quality of the population and increasing susceptibility for the unfavourable course of acute infections. It has been observed that excess body mass significantly influences the COVID-19 outcome. The aim of this review is to present the latest scientific reports on the impact of excess body mass on the course and complications of COVID-19. The Web of Science, PubMed, and Google Scholar databases were searched. Only studies reporting patients stated to be COVID-19 positive based on the results of a nasopharyngeal swab and the ribonucleic acid test were included. It is shown that thromboembolic and ischemic complications, namely stroke, disseminated intravascular coagulation, severe hyperglycaemia, and leukoencephalopathy are more likely to appear in COVID-19 positive patients with obesity compared to non-obese subjects. COVID-19 complications such as cardiomyopathy, dysrhythmias, endothelial dysfunction, acute kidney injury, dyslipidaemia, lung lesions and acute respiratory distress syndrome have a worse outcome among obese patients.
Demonstration of Co-Infection and Trans-Encapsidation of Viral RNA In Vitro Using Epitope-Tagged Foot-and-Mouth Disease Viruses
Authors: Childs Kay , Juleff Nicholas , Moffat Katy , Seago Julian
Published: December 2021

Foot-and-mouth disease, caused by foot-and-mouth disease virus (FMDV), is an economically devastating disease affecting several important livestock species. FMDV is antigenically diverse and exists as seven serotypes comprised of many strains which are poorly cross-neutralised by antibodies induced by infection or vaccination. Co-infection and recombination are important drivers of antigenic diversity, especially in regions where several serotypes co-circulate at high prevalence, and therefore experimental systems to study these events in vitro would be beneficial. Here we have utilised recombinant FMDVs containing an HA or a FLAG epitope tag within the VP1 capsid protein to investigate the products of co-infection in vitro. Co-infection with viruses from the same and from different serotypes was demonstrated by immunofluorescence microscopy and flow cytometry using anti-tag antibodies. FLAG-tagged VP1 and HA-tagged VP1 could be co-immunoprecipitated from co-infected cells, suggesting that newly synthesised capsids may contain VP1 proteins from both co-infecting viruses. Furthermore, we provide the first demonstration of trans-encapsidation of an FMDV genome into capsids comprised of proteins encoded by a co-infecting heterologous virus. This system provides a useful tool for investigating co-infection dynamics in vitro, particularly between closely related strains, and has the advantage that it does not depend upon the availability of strain-specific FMDV antibodies.
ATM-Dependent Phosphorylation of Hepatitis B Core Protein in Response to Genotoxic Stress
Authors: Lubyova Barbora , Tikalova Eva , Krulova Kristyna , Hodek Jan , Zabransky Ales , Hirsch Ivan , Weber Jan
Published: December 2021

Chronic hepatitis caused by infection with the Hepatitis B virus is a life-threatening condition. In fact, 1 million people die annually due to liver cirrhosis or hepatocellular carcinoma. Recently, several studies demonstrated a molecular connection between the host DNA damage response (DDR) pathway and HBV replication and reactivation. Here, we investigated the role of Ataxia-telangiectasia-mutated (ATM) and Ataxia telangiectasia and Rad3-related (ATR) PI3-kinases in phosphorylation of the HBV core protein (HBc). We determined that treatment of HBc-expressing hepatocytes with genotoxic agents, e.g., etoposide or hydrogen peroxide, activated the host ATM-Chk2 pathway, as determined by increased phosphorylation of ATM at Ser1981 and Chk2 at Thr68. The activation of ATM led, in turn, to increased phosphorylation of cytoplasmic HBc at serine-glutamine (SQ) motifs located in its C-terminal domain. Conversely, down-regulation of ATM using ATM-specific siRNAs or inhibitor effectively reduced etoposide-induced HBc phosphorylation. Detailed mutation analysis of S-to-A HBc mutants revealed that S170 (S168 in a 183-aa HBc variant) is the primary site targeted by ATM-regulated phosphorylation. Interestingly, mutation of two major phosphorylation sites involving serines at positions 157 and 164 (S155 and S162 in a 183-aa HBc variant) resulted in decreased etoposide-induced phosphorylation, suggesting that the priming phosphorylation at these serine-proline (SP) sites is vital for efficient phosphorylation of SQ motifs. Notably, the mutation of S172 (S170 in a 183-aa HBc variant) had the opposite effect and resulted in massively up-regulated phosphorylation of HBc, particularly at S170. Etoposide treatment of HBV infected HepG2-NTCP cells led to increased levels of secreted HBe antigen and intracellular HBc protein. Together, our studies identified HBc as a substrate for ATM-mediated phosphorylation and mapped the phosphorylation sites. The increased expression of HBc and HBe antigens in response to genotoxic stress supports the idea that the ATM pathway may provide growth advantage to the replicating virus.
Development of a Kit for Rapid Immunochromatographic Detection of Sacbrood Virus Infecting Apis cerana (AcSBV) Based on Polyclonal and Monoclonal Antibodies Raised against Recombinant VP1 and VP2 Expressed in Escherichia coli
Authors: Lee Song Hee , Oh Tae-Kyun , Oh Sung , Kim Seongdae , Noh Han Byul , Vinod Nagarajan , Lee Ji Yoon , Moon Eun Sun , Choi Chang Won
Published: December 2021

A Korean isolate of the sacbrood virus infecting Apis cerana (AcSBV-Kor) is the most destructive honeybee virus, causing serious economic damage losses in Korean apiculture. To address this, here, we attempted to develop an assay for the rapid detection of AcSBV-Kor based on immunochromatographic detection of constituent viral proteins. Genes encoding VP1 and VP2 proteins of AcSBV-Kor were cloned into an expression vector (pET-28a) and expressed in Escherichia coli BL21(DE3). During purification, recombinant VP1 (rVP1) and VP2 (rVP2) proteins were found in the insoluble fraction, with a molecular size of 26.7 and 24.9 kDa, respectively. BALB/c mice immunized with the purified rVP1 and rVP2 produced polyclonal antibodies (pAbs) such as pAb-rVP1 and pAb-rVP2. Western blot analysis showed that pAb-rVP1 strongly reacted with the homologous rVP1 but weakly reacted with heterologous rVP2. However, pAb-rVP2 strongly reacted not only with the homologous rVP2 but also with the heterologous rVP1. Spleen cells of the immunized mice fused with SP2/0-Ag14 myeloma cells produced monoclonal antibodies (mAbs) such as mAb-rVP1-1 and mAb-rVP2-13. Western blot analysis indicated that pAb-rVP1, pAb-rVP2, mAb-rVP1-1, and mAb-rVP2-13 reacted with AcSBV-infected honeybees and larvae as well as the corresponding recombinant proteins. These antibodies were then used in the development of a rapid immunochromatography (IC) strip assay kit with colloidal gold coupled to pAb-rVP1 and pAb-rVP2 at the conjugate pad and mAb-rVP1-1 and mAb-rVP2-13 at the test line. One antibody pair, pAb-rVP1/mAb-VP1-1, showed positive reactivity as low as 1.38 × 103 copies, while the other pair, pAb-rVP2/mAb-VP2-13, showed positive reactivity as low as 1.38 × 104 copies. Therefore, the antibody pair pAb-rVP1/mAb-VP1-1 was selected as a final candidate for validation. To validate the detection of AcSBV, the IC strip tests were conducted with 50 positive and 50 negative samples and compared with real-time PCR tests. The results confirm that the developed IC assay is a sufficiently sensitive and specific detection method for user-friendly and rapid detection of AcSBV.
Protective Immunity against Gamma and Zeta Variants after Inactivated SARS-CoV-2 Virus Immunization
Authors: Fumagalli Marcilio Jorge , Castro-Jorge Luiza Antunes , Fraga-Silva Thais Fernanda de Campos , de Azevedo Patrick Orestes , Capato Carlos Fabiano , Rattis Bruna Amanda Cruz , Hojo-Souza Natália Satchiko , Floriano Vitor Gonçalves , de Castro Julia Teixeira , Ramos Simone Gusmão , da Fonseca Benedito Antônio Lopes , Bonato Vânia Luiza Deperon , Gazzinelli Ricardo Tostes , Figueiredo Luiz Tadeu Moraes
Published: December 2021

The persistent circulation of SARS-CoV-2 represents an ongoing global threat due to the emergence of new viral variants that can sometimes evade the immune system of previously exposed or vaccinated individuals. We conducted a follow-up study of adult individuals that had received an inactivated SARS-CoV-2 vaccine, evaluating antibody production and neutralizing activity over a period of 6 months. In addition, we performed mice immunization with inactivated SARS-CoV-2, and evaluated the immune response and pathological outcomes against Gamma and Zeta variant infection. Vaccinated individuals produced high levels of antibodies with robust neutralizing activity, which was significantly reduced against Gamma and Zeta variants. Production of IgG anti-S antibodies and neutralizing activity robustly reduced after 6 months of vaccination. Immunized mice demonstrated cellular response against Gamma and Zeta variants, and after viral infection, reduced viral loads, IL-6 expression, and histopathological outcome in the lungs. TNF levels were unchanged in immunized or not immunized mice after infection with the Gamma variant. Furthermore, serum neutralization activity rapidly increases after infection with the Gamma and Zeta variants. Our data suggest that immunization with inactivated WT SARS-CoV-2 induces a promptly responsive cross-reactive immunity response against the Gamma and Zeta variants, reducing COVID-19 pathological outcomes.
Porcine Deltacoronavirus Utilizes Sialic Acid as an Attachment Receptor and Trypsin Can Influence the Binding Activity
Authors: Yuan Yixin , Zu Shaopo , Zhang Yunfei , Zhao Fujie , Jin Xiaohui , Hu Hui
Published: December 2021

Porcine deltacoronavirus (PDCoV) is a novel coronavirus that causes diarrhea in nursing piglets. Studies showed that PDCoV uses porcine aminopeptidase N (pAPN) as an entry receptor, but the infection of pAPN-knockout cells or pigs with PDCoV revealed that pAPN might be not a critical functional receptor, implying there exists an unidentified receptor involved in PDCoV infection. Herein, we report that sialic acid (SA) can act as an attachment receptor for PDCoV invasion and facilitate its infection. We first demonstrated that the carbohydrates destroyed on the cell membrane using NaIO4 can alleviate the susceptibility of cells to PDCoV. Further study showed that the removal of SA, a typical cell-surface carbohydrate, could influence the PDCoV infectivity to the cells significantly, suggesting that SA was involved in the infection. The results of plaque assay and Western blotting revealed that SA promoted PDCoV infection by increasing the number of viruses binding to SA on the cell surface during the adsorption phase, which was also confirmed by atomic force microscopy at the microscopic level. In in vivo experiments, we found that the distribution levels of PDCoV and SA were closely relevant in the swine intestine, which contains huge amount of trypsin. We further confirmed that SA-binding capacity to PDCoV is related to the pre-treatment of PDCoV with trypsin. In conclusion, SA is a novel attachment receptor for PDCoV infection to enhance its attachment to cells, which is dependent on the pre-treatment of trypsin on PDCoV. This study paves the way for dissecting the mechanisms of PDCoV–host interactions and provides new strategies to control PDCoV infection.
Fc-Mediated E2-Dimer Subunit Vaccines of Atypical Porcine Pestivirus Induce Efficient Humoral and Cellular Immune Responses in Piglets
Authors: Ren Xujiao , Qian Ping , Liu Shudan , Chen Huanchun , Li Xiangmin
Published: December 2021

Congenital tremor (CT) type A-II in piglets is caused by an emerging atypical porcine pestivirus (APPV), which is prevalent in swine herds and a serious threat to the pig production industry. This study aimed to construct APPV E2 subunit vaccines fused with Fc fragments and evaluate their immunogenicity in piglets. Here, APPV E2Fc and E2ΔFc fusion proteins expressed in Drosophila Schneider 2 (S2) cells were demonstrated to form stable dimers in SDS-PAGE and western blotting assays. Functional analysis revealed that aE2Fc and aE2ΔFc fusion proteins could bind to FcγRI on antigen-presenting cells (APCs), with the affinity of aE2Fc to FcγRI being higher than that of aE2ΔFc. Moreover, subunit vaccines based on aE2, aE2Fc, and aE2ΔFc fusion proteins were prepared, and their immunogenicity was evaluated in piglets. The results showed that the Fc fusion proteins emulsified with the ISA 201VG adjuvant elicited stronger humoral and cellular immune responses than the IMS 1313VG adjuvant. These findings suggest that APPV E2 subunit vaccines fused with Fc fragments may be a promising vaccine candidate against APPV.
Mid-Regional Pro-Adrenomedullin, Methemoglobin and Carboxyhemoglobin as Prognosis Biomarkers in Critically Ill Patients with COVID-19: An Observational Prospective Study
Authors: Oblitas Crhistian-Mario , Galeano-Valle Francisco , Ramírez-Navarro Jesús , López-Cano Jorge , Monterrubio-Manrique Ángel , García-Gámiz Mercedes , Sancho-González Milagros , Arenal-López Sara , Álvarez-Sala Walther Luis-Antonio , Demelo-Rodríguez Pablo
Published: December 2021

Mid-regional pro-adrenomedullin (MR-proADM), methemoglobin (MetHb), and carboxyhemoglobin (COHb) levels have been associated with sepsis. In this study, we assessed the role of this potential biomarkers in critically ill COVID-19 patients. Outcomes were mortality and a combined event (mortality, venous or arterial thrombosis, and orotracheal intubation (OTI)) during a 30-day follow-up. A total of 95 consecutive patients were included, 51.6% required OTI, 12.6% patients died, 8.4% developed VTE, and 3.1% developed arterial thrombosis. MetHb and COHb levels were not associated with mortality nor combined event. Higher MR-proADM levels were found in patients with mortality (median of 1.21 [interquartile range-IQR-0.84;2.33] nmol/L vs. 0.76 [IQR 0.60;1.03] nmol/L, p = 0.011) and combined event (median of 0.91 [IQR 0.66;1.39] nmol/L vs. 0.70 [IQR 0.51;0.82] nmol/L, p < 0.001); the positive likelihood ratio (LR+) and negative likelihood ratio (LR−) for mortality were 2.40 and 0.46, respectively. The LR+ and LR− for combined event were 3.16 and 0.63, respectively. MR-proADM ≥1 nmol/L was the optimal cut-off for mortality and combined event prediction. The predictive capacity of MR-proADM showed an area under the ROC curve of 0.73 (95% CI, 0.62–0.81) and 0.72 (95% CI, 0.62–0.81) for mortality and combined event, respectively. In conclusion, elevated on-admission MR-proADM levels were associated with higher risk of 30-day mortality and 30-day poor outcomes in a cohort of critically ill patients with COVID-19.
An Outbreak in Pigeons Caused by the Subgenotype VI.2.1.2 of Newcastle Disease Virus in Brazil
Authors: Thomazelli Luciano M. , Sinhorini Juliana A. , Oliveira Danielle B. L. , Knöbl Terezinha , Bosqueiro Tatiana C. M. , Sano Elder , Costa Gladyston C. V. , Monteiro Cairo , Dorlass Erick G. , Utecht Nathalia , Scagion Guilherme P. , Meneguin Carla , Silva Laura M. N. , Moraes Maria Vitória S. , Bueno Larissa M. , Reischak Dilmara , Carrasco Adriano O. T. , Arns Clarice W. , Ferreira Helena L. , Durigon Edison L.
Published: December 2021

Newcastle disease virus (NDV) can infect over 250 bird species with variable pathogenicity; it can also infect humans in rare cases. The present study investigated an outbreak in feral pigeons in São Paulo city, Brazil, in 2019. Affected birds displayed neurological signs, and hemorrhages were observed in different tissues. Histopathology changes with infiltration of mononuclear inflammatory cells were also found in the brain, kidney, proventriculus, heart, and spleen. NDV staining was detected by immunohistochemistry. Twenty-seven out of thirty-four tested samples (swabs and tissues) were positive for Newcastle disease virus by RT-qPCR test, targeting the M gene. One isolate, obtained from a pool of positive swab samples, was characterized by the intracerebral pathogenicity index (ICPI) and the hemagglutination inhibition (HI) tests. This isolate had an ICPI of 0.99, confirming a virulent NDV strain. The monoclonal antibody 617/161, which recognizes a distinct epitope in pigeon NDV strains, inhibited the isolate with an HI titer of 512. A complete genome of NDV was obtained using next-generation sequencing. Phylogenetic analysis based on the complete CDS F gene grouped the detected isolate with other viruses from subgenotype VI.2.1.2, class II, including one previously reported in Southern Brazil in 2014. This study reports a comprehensive characterization of the subgenotype VI.2.1.2, which seems to have been circulating in Brazilian urban areas since 2014. Due to the zoonotic risk of NDV, virus surveillance in feral pigeons should also be systematically performed in urban areas.
Clinical Manifestation of Subacute Thyroiditis Triggered by SARS-CoV-2 Infection Can Be HLA-Dependent
Authors: Stasiak Magdalena , Zawadzka-Starczewska Katarzyna , Lewiński Andrzej
Published: December 2021

In the last two years, we have been struggling with the pandemic of SARS-CoV-2, the virus causing COVID-19. Several cases of subacute thyroiditis (SAT) have already been described as directly related to SARS-CoV-2 infection. The clinical course of SAT induced by SARS-CoV-2 can be entirely different from the classic SAT course, and one of the most important differences is a very rapid SAT onset observed in some patients, especially a phenomenon of the simultaneous presence of both diseases. The aim of this report is to compare HLA profile and clinical course of SAT in four patients, in whom SAT was considered as triggered by COVID-19, with special attention paid to the differences between a patient with rare simultaneous presence of SAT and COVID-19, and patients with longer time lag between the diseases. The unusual phenomenon of simultaneous occurrence of COVID-19 and SAT induced by SARS-CoV-2 infection can be HLA-dependent and related to the presence of homozygosity at HLA-B*35. Additionally, the clinical course of SAT triggered by COVID-19 can be HLA-related in regard to the risk of recurrence, and to a variety of other aspects, including severity of thyrotoxicosis.
Determining Economical Irrigation Depths in a Sandy Field Using a Combination of Weather Forecast and Numerical Simulation
Authors: Abd El Baki Hassan M. , Fujimaki Haruyuki
Published: December 2021

Advancement of modern technologies has given numerical simulations a crucial role to effectively manage irrigation. A new numerical scheme to determine irrigation depths was incorporated into WASH 2D, which is a numerical simulation model of crop response to irrigation. Based on two predicted points of cumulative transpiration—water price and quantitative weather forecast—the scheme can optimize an irrigation depth in which net income is maximized. A field experiment was carried out at the Arid Land Research Center, Tottori, Japan, in 2019, to evaluate the effectiveness of the scheme on net income and crop production compared to a tensiometer-based automated irrigation system. Sweetcorn (Zea mays L., Amaenbou 86) was grown in three water balance lysimeters per each treatment, filled with sandy soil. The scheme could achieve a 4% higher net income, due to a 7% increase in green fodder yield, and an 11% reduction in irrigation amount, compared with the automated irrigation method. These results indicate that the numerical scheme, in combination with quantitative weather forecasts, can be a useful tool to determine irrigation depths, maximize net incomes which are farmers’ targets, and avoid large investments that are required for the automated irrigation system.
Heavy Metals and Microbes Accumulation in Soil and Food Crops Irrigated with Wastewater and the Potential Human Health Risk: A Metadata Analysis
Authors: Othman Yahia A. , Al-Assaf Amani , Tadros Maher J. , Albalawneh Abeer
Published: December 2021

Wastewater is actively used for irrigation of vegetable and forage crops in arid lands due to water scarcity and cost advantages. The objective of this review was to assess the effect of wastewater (mixture sources) reuse in irrigation on soil, crop (vegetable and forage crops), animal products, and human health. The metadata analysis of 95 studies revealed that the mean of toxic heavy metals including nickel (Ni), chromium (Cr), cadmium (Cd), lead (Pb), and zinc (Zn) in untreated wastewater were higher than the world standard limits in wastewater-irrigated regions. Although heavy metals in treated wastewater were within the standard limits in those areas, the concentration of those toxic elements (Pb, Cd, Ni, Cr, and As) exceeded the allowable limits in both soil and vegetables’ edible parts. In fact, the concentration of heavy metals in vegetables’ edible parts increased by 3–9 fold when compared with those irrigated with fresh water. Escherichia coli in wastewater-irrigated soil was about 2 × 106 (CFU g−1) and about 15 (CFU g−1) in vegetables’ edible parts (leaf, bulb, tuber and fruit) while the mean total coliforms was about 1.4 × 106 and 55 (CFU g−1) in soil and vegetables’ edible parts, respectively. For human health risk assessment, the estimated daily intake (EDI) and human health risk index (HRI) ranged from 0.01 to 8 (EDI and HRI > 1.0 associated with adverse health effects). Although the mean of EDI for heavy metals from wastewater-irrigated vegetables were less than 1, the HRI for Cd and Pb were above the limits for safe consumption. Overall, heavy metal levels in wastewater that used for irrigation of agricultural crops could be within the recommended levels by the world standards, but the long-term use of this reused water will contaminate soil and crops with several toxic heavy metals leading to potential carcinogenic risks to humans. Therefore, rigorous and frequent testing (wastewater, soil, and plant) is required in cultivated farms to prevent the translocation of heavy metals in the food chain.
Policy, Technology, and Management Options for Water Conservation in the Ogallala Aquifer in Kansas, USA
Authors: Steiner Jean L. , Devlin Daniel L. , Perkins Sam , Aguilar Jonathan P. , Golden Bill , Santos Eduardo A. , Unruh Matt
Published: December 2021

The Ogallala Aquifer underlies 45 million ha, providing water for approximately 1.9 million people and supporting the robust agriculture economy of the US Great Plains region. The Ogallala Aquifer has experienced severe depletion, particularly in the Southern Plains states. This paper presents policy innovations that promote adoption of irrigation technology, and management innovations. Innovation in Kansas water policy has had the dual effects of increasing the authority of the state to regulate water while also providing more flexibility and increasing local input to water management and regulation. Technology innovations have focused on improved timing and placement of water. Management innovations include soil water monitoring, irrigation scheduling, soil health management and drought-tolerant varieties, crops, and cropping systems. The most noted success has been in the collective action which implemented a Local Enhanced Management Area (LEMA), which demonstrated that reduced water pumping resulted in low to no groundwater depletion while maintaining net income. Even more encouraging is the fact that irrigators who have participated in the LEMA or other conservation programs have conserved even more water than their goals. Innovative policy along with creative local–state–federal and private–public partnerships are advancing irrigation technology and management. Flexibility through multi-year allocations, banking of water not used in a given year, and shifting water across multiple water rights or uses on a farm are promising avenues to engage irrigators toward more sustainable irrigation in the Ogallala region.
Monitoring of the Operating Membrane Condition Using PZT Based EMI of External Steel Pipe
Authors: Kim Junkyeong , Eom Jungyeol , Lee Sangyoup , Lee Yong-Soo , Kim Hyung-Soo
Published: December 2021

Membrane systems are increasingly being used for treating water, wastewater, and reused water. However, membrane damage can decrease removal efficiency and hinder downstream applicability. Thus, the operating conditions of the membrane should be monitored. This study monitored the operating conditions of the membrane using lead zirconate titanate (PZT)-based electro-mechanical impedance (EMI) measurements in an external air pipe. Pilot-scale tests were performed to verify the performance of the proposed method. A pressure decay test (PDT) was performed using a PZT-attached air pipe, in which the pressure was measured using PZT, and a pressure gauge was employed to measure the reference pressure. The EMI signals changed according to the variations in the pressure inside the steel air pipe. To index the signal variation, the amplitude of the major peak was extracted and compared with the reference pressure. The amplitude of the major peak was inversely proportional to the pressure change. The pressure estimation equation was derived using a linear regression between the amplitudes of the major peak and the reference pressures. According to the results, the proposed monitoring system that utilizes the EMI of an external steel pipe is a potential solution to improve the sensitivity and speed of the PDT.
Improving Design by Partnering in Engineering–Procurement–Construction (EPC) Hydropower Projects: A Case Study of a Large-Scale Hydropower Project in China
Authors: Liu Yang , Tang Wenzhe , Duffield Colin F. , Hui Felix Kin Peng , Zhang Lihai , Zhang Xuteng , Kang Yanling
Published: December 2021

Hydropower, as a renewable energy resource, has become an important way to fit for Chinese long-term energy policy of energy transformation. Engineering–procurement–construction (EPC) has been increasingly adopted for improving hydropower project delivery efficiency in the utilization of water resources and generation of clean energy, where design plays a critical role in project success. Existing studies advocate the need to use partnering for better solutions to designs in EPC hydropower projects. However, there is a lack of a theoretical framework to systematically address design-related issues considering different participants’ interactions. This study coherently examined the causal relationships among partnering, design management, design capability, and EPC hydropower project performance by establishing and validating a conceptual model, with the support of data collected from a large-scale EPC hydropower project. Path analysis reveals that partnering can directly promote design management and design capability and exert an effect on design capability through enhancing design management, thereby achieving better hydropower project outcomes. This study’s contribution lies in that it theoretically builds the links between intra- and inter-organizational design-related activities by systematically mapping EPC hydropower project performance on partnering, design management, and design capability. These findings also suggest broad practical strategies for participants to optimally integrate their complementary resources into designs to achieve superior hydropower project performance.
Drought Monitoring over Nepal for the Last Four Decades and Its Connection with Southern Oscillation Index
Authors: Bagale Damodar , Sigdel Madan , Aryal Deepak
Published: December 2021

This study identified summer and annual drought events using the Standard Precipitation Index (SPI) for 107 stations across Nepal from 1977 to 2018. For this, frequency, duration, and severity of drought events were investigated. The SPI4 and SPI12 time scales were interpolated to illustrate the spatial patterns of major drought episodes and their severity. A total of 13 and 24 percent of stations over the country showed a significant decreasing trend for SPI4 and SPI12. Droughts were recorded during El Niño and non-El Niño years in Nepal. Among them, 1992 was the worst drought year, followed by the drought year, 2015. More than 44 percent of the locations in the country were occupied under drought conditions during these extreme drought events. Droughts have been recorded more frequently in Nepal since 2005. The areas of Nepal affected by extreme, severe, and moderate drought in summer were 8, 9, and 18 percent, while during annual events they were 7, 11, and 17 percent, respectively. Generally, during the drought years, the SPI and Southern Oscillation Index (SOI) have a strong phase relation compared to the average years.
Water Resource Recovery Facilities (WRRFs): The Case Study of Palermo University (Italy)
Authors: Mannina Giorgio , Alduina Rosa , Badalucco Luigi , Barbara Lorenzo , Capri Fanny Claire , Cosenza Alida , Di Trapani Daniele , Gallo Giuseppe , Laudicina Vito Armando , Muscarella Sofia Maria , Presti Dario
Published: December 2021

The wastewater sector paradigm is shifting from wastewater treatment to resource recovery. In addition, concerns regarding sustainability during the operation have increased. In this sense, there is a need to break barriers (i.e., social, economic, technological, legal, etc.) for moving forward towards water resource recovery facilities and demonstration case studies can be very effective and insightful. This paper presents a new water resource recovery case study which is part of the Horizon 2020 EU Project “Achieving wider uptake of water-smart solutions—Wider Uptake”. The final aim is to demonstrate the importance of a resource recovery system based on the circular economy concept. The recovery facilities at Palermo University (Italy) are first presented. Afterwards, the resource recovery pilot plants are described. Preliminary results have underlined the great potential of the wastewater treatment plant in terms of resources recovery and the central role of the University in fostering the transition towards circular economy. The fermentation batch test highlighted a volatile fatty acids (VFAs) accumulation suitable for polyhydroxyalkanoates (PHAs) production. The results of static adsorption and desorption tests showed that the highest amount of adsorbed NH4+ was recorded for untreated and HCl-Na treated clinoptilolite.
Effect of Precipitation on Location Choice of Foreign Direct Investment in China
Authors: Xu Zhiyuan , Zhu Yuting , Yang Yongliang
Published: December 2021

This paper studies the effect of precipitation on the location of foreign direct investment (FDI) based on city-level data of China from 2003 to 2018. The results show that precipitation has a significant promoting effect on the regional agglomeration of FDI. This indicates that FDI location selection is more inclined to use the dilution ability of precipitation for pollution to reduce environmental costs, rather than relying solely on water resources. Further analysis shows that the preference of FDI enterprises on precipitation in the eastern region is significantly lower than that in the central and northeastern regions. This reflects the trend that FDI enterprises gradually shift to regions with a low degree of environmental regulation to reduce environmental costs. Therefore, the efforts made by economically developed cities to improve the regional ecological environment may be offset by the location adjustment of FDI enterprises, and precipitation has become an important stimulus for the location transfer of FDI enterprises.
The Sustainable Treatment Effect of Constructed Wetland for the Aquaculture Effluents from Blunt Snout Bream (Megalobrama amblycephala) Farm
Authors: Li Bing , Jia Rui , Hou Yiran , Zhang Chengfeng , Zhu Jian , Ge Xianping
Published: December 2021

In aquaculture, constructed wetland (CW) has recently attracted attention for use in effluent purification due to its low running costs, high efficiency and convenient operation,. However, less data are available regarding the long-term efficiency of farm-scale CW for cleaning effluents from inland freshwater fish farms. This study investigated the effectiveness of CW for the removal of nutrients, organic matter, phytoplankton, heavy metals and microbial contaminants in effluents from a blunt snout bream (Megalobrama amblycephala) farm during 2013–2018. In the study, we built a farm-scale vertical subsurface flow CW which connected with a fish pond, and its performance was evaluated during the later stage of fish farming. The results show that CW improved the water quality of the fish culture substantially. This system was effective in the removal of nutrients, with a removal rate of 21.43–47.19% for total phosphorus (TP), 17.66–53.54% for total nitrogen (TN), 32.85–53.36% for NH4+-N, 33.01–53.28% NH3-N, 30.32–56.01% for NO3−-N and 42.75–63.85% for NO2−-N. Meanwhile, the chlorophyll a (Chla) concentration was significantly reduced when the farming water flowed through the CW, with a 49.69–62.01% reduction during 2013–2018. However, the CW system only had a modest effect on the chemical oxygen demand (COD) in the aquaculture effluents. Furthermore, concentrations of copper (Cu) and lead (Pb) were reduced by 39.85% and 55.91%, respectively. A microbial contaminants test showed that the counts of total coliform (TC) and fecal coliform (FC) were reduced by 55.93% and 48.35%, respectively. In addition, the fish in the CW-connected pond showed better growth performance than those in the control pond. These results indicate that CW can effectively reduce the loads of nutrients, phytoplankton, metals, and microbial contaminants in effluents, and improve the water quality of fish ponds. Therefore, the application of CW in intensive fish culture systems may provide an advantageous alternative for achieving environmental sustainability.
A Comparison of Methods to Address Anaerobic Conditions in Rainwater Harvesting Systems
Authors: Gee Kathy DeBusk , Schimoler Daniel , Charron Bree T. , Woodward Mitch D. , Hunt William F.
Published: December 2021

Although historically used in semi-arid and arid regions, rainwater harvesting (RWH) systems have increasingly been used in non-arid and humid regions of the world to conserve potable water and mitigate stormwater runoff. Rainfall characteristics and usage patterns of stored rainwater are distinctly different in (semi-)arid and humid regions, thus presenting a unique set of challenges with respect to their utilization. Coupled with infrequent use, the addition of nitrogen and organic matter via pollen during the spring season can lead to anaerobic conditions within storage tanks, which hinders nitrogen removal, gives stored water an offensive odor, and ultimately discourages use of the water. This study evaluated three measures that can be implemented for new and existing RWH systems to prevent the development of anaerobic conditions within storage tanks: first flush diversion, simulated use, and the continuous circulation of stored water. Study findings indicate that preventing anaerobic conditions via simulated use and recirculation (1) does not necessarily remedy the issue of poor aesthetics within rainwater storage tanks, and (2) can decrease the water quality benefits provided by these systems. Rather, preventing the introduction of pollen and particulate matter to the storage tank via a first flush diverter and minimizing disturbance of settled material in the tank appear to be the most effective methods of addressing the poor aesthetics and odor problems associated with anaerobic conditions.