niryuu/sni-each-converted huggingface dataset:
Background: Nonantibiotic alternatives providing local gut immunity have been recommended for managing calf diarrhea. Animals: One hundred and two calves with diarrhea. Hypothesis: Oral supplementation with immunoglobulins in calves with diarrhea will reduce time to resolution of diarrhea, number of treatment events, and mortality rate. Methods: Randomized controlled trial. Calves were assigned into 1 of 3 groups. The treatment group was supplemented with 20 g of immunoglobulins in milk twice daily for 14 days. The placebo group was supplemented with 20 g of a product with similar nutritional value as the treatment group, but without immunoglobulins, in milk, twice daily for 14 days. The control group received no supplements. Medical treatments, time to resolution of diarrhea, and case fatality rates were compared. Results: There was no difference in the proportion of treatment events (treatment, 79% versus placebo, 77% versus control, 71%) among groups (P = .69). The median time to resolution of diarrhea was not different between the treatment (10.5 days; 95% confidence interval [CI], 7, 13) and control (8 days; 95% CI, 5, 10) groups (P = .08) or between the placebo (6.5 days; 95% CI, 3, 9) and control groups (P = .89). Median time to resolution was shorter (P = .008) in the placebo compared to the treatment group (6.5 versus 10.5 days). Case fatality rates among groups (treatment, 12% versus placebo, 3% versus control, 3%) were not different (P = .36). Conclusions and Clinical Importance: Expected benefits of conferring local gut immunity by immunoglobulin supplementation in calves with diarrhea were not evident. cattle, colostrum, fecal score, immunity, milk
Output: Randomized controlled clinical trial on the effect of oral immunoglobulin supplementation on neonatal dairy calves with diarrhea
Cyclophilin A (CypA) is a ubiquitous cis-trans prolyl isomerase with key roles in immunity and viral infection. CypA suppresses T-cell activation through cyclosporine complexation and is required for effective HIV-1 replication in host cells. We show that CypA is acetylated in diverse human cell lines and use a synthetically evolved acetyllysyl-tRNA synthetase/tRNA CUA pair to produce recombinant acetylated CypA in Escherichia coli. We determined atomic-resolution structures of acetylated CypA and its complexes with cyclosporine and HIV-1 capsid. Acetylation markedly inhibited CypA catalysis of cis to trans isomerization and stabilized cis rather than trans forms of the HIV-1 capsid. Furthermore, CypA acetylation antagonized the immunosuppressive effects of cyclosporine by inhibiting the sequential steps of cyclosporine binding and calcineurin inhibition. Our results reveal that acetylation regulates key functions of CypA in immunity and viral infection and provide a general set of mechanisms by which acetylation modulates interactions to regulate cell function.
Output: acetylation regulates Cyclophilin a catalysis, immunosuppression and HIV isomerization
Chemically synthesized short interfering RNA (siRNA) of pre-determined sequence has ushered a new era in the application of RNA interference (RNAi) against viral genes. We have paid particular attention to respiratory viruses that wreak heavy morbidity and mortality worldwide. The clinically significant ones include respiratory syncytial virus (RSV), parainfluenza virus (PIV) and influenza virus. As the infection by these viruses is clinically restricted to the respiratory tissues, mainly the lungs, the logical route for the application of the siRNA was also the same, i.e., via the nasal route. Following the initial success of intranasal siRNA against RSV, second-generation siRNAs were made against the viral polymerase large subunit (L) that were chemically modified and screened for improved stability, activity and pharmacokinetics. 2 ′ -Omethyl (2 ′ -O -Me) and 2 ′ -deoxy-2 ′ -fluoro (2 ′ -F) substitutions in the ribose ring were incorporated in different positions of the sense and antisense strands and the resultant siRNAs were tested with various transfection reagents intranasally against RSV. Based on these results, we propose the following consensus for designing intranasal antiviral siRNAs: (i) modified 19-27 nt long double-stranded siRNAs are functional in the lung, (ii) excessive 2 ′ -OMe and 2 ′ -F modifications in either or both strands of these siRNAs reduce efficacy, and (iii) limited modifications in the sense strand are beneficial, although their precise efficacy may be position-dependent.
Output: Chapter 16 Treating Respiratory Viral Diseases with Chemically Modified, Second Generation Intranasal siRNAs
The lengthy duration of multidrug therapy needed to cure tuberculosis (TB) poses significant challenges for global control of the disease. Moreover, chronic inflammation associated with TB leads to pulmonary damage that can remain even after successful cure. Thus, there is a great need for the development of effective shorter drug regimens to improve clinical outcome and strengthen TB control. Host-directed therapy (HDT) is emerging as a novel adjunctive strategy to enhance the efficacy and shorten the duration of TB treatment. Previously, we showed that the administration of CC-3052, a phosphodiesterase-4 inhibitor (PDE4i), reduced the host inflammatory response during Mycobacterium tuberculosis (Mtb) infection and improved the antimicrobial efficacy of isoniazid (INH) in both the mouse and rabbit models. In the present study, we evaluated the pharmacokinetics and explored the mechanism underlying the efficacy of a more potent PDE4i, CC-11050, as adjunct to INH treatment in a mouse model of pulmonary Mtb infection. Genome-wide lung transcriptome analysis confirmed the dampening of inflammation and associated network genes that we previously reported with CC-3052. Consistent with the reduction in inflammation, a significant improvement in Mtb control and pathology was observed in the lungs of mice treated with CC-11050 plus INH, compared to INH alone. This important confirmatory study will be used to help design upcoming human clinical trials with CC-11050 as an HDT for TB treatment.
Output: Pharmacologic inhibition of host Phosphodiesterase-4 improves isoniazid-Mediated clearance of Mycobacterium tuberculosis
The countries of Association of South-East Asian Nations (ASEAN) have agreed to the formation of open skies within the region. Member countries differ widely in terms of their GDP per capita, their size, aviation policies and the strength of their aviation industries. Granted these differences, several possibilities for facilitating the move are examined. These include taking an economic approach to aviation negotiations, liberalising within sub-regional groupings, a staged framework of liberalisation, and increasing the scope for lowcost carriers to compete, possibly through development of secondary markets. Moves will also necessitate attention being given to complementary issues, such as competition and subsidy policies and ownership. r
Output: Open Skies in ASEAN
Background: Plausible disasters may yield hundreds or thousands of critically ill victims. However, most countries, including those with widely available critical care services, lack sufficient specialized staff, medical equipment, and ICU space to provide timely, usual critical care for a large influx of additional patients. Shifting critical care disaster preparedness efforts to augment limited, essential critical care (emergency mass critical care [EMCC]), rather than to marginally increase unrestricted, individual-focused critical care may provide many additional people with access to life-sustaining interventions. In 2007, in response to the increasing concern over a severe influenza pandemic, the Task Force on Mass Critical Care (hereafter called the Task Force) convened to suggest the essential critical care therapeutics and interventions for EMCC. Task Force suggestions: EMCC should include the following: (1) mechanical ventilation, (2) IV fluid resuscitation, (3) vasopressor administration, (4) medication administration for specific disease states (eg, antimicrobials and antidotes), (5) sedation and analgesia, and (6) select practices to reduce adverse consequences of critical illness and critical care delivery. Also, all hospitals with ICUs should prepare to deliver EMCC for a daily critical care census at three times their usual ICU capacity for up to 10 days. Discussion: By using the Task Force suggestions for EMCC, communities may better prepare to deliver augmented critical care in response to disasters. In light of current mass critical care data limitations, the Task Force suggestions were developed to guide preparedness but are not intended as strict policy mandates. Additional research is required to evaluate EMCC and revise the strategy as warranted. Key words: critical care surge capacity; disaster medicine; influenza pandemic; mass casualty medical care; medical surge capacity Abbreviations: ED ϭ emergency department; EMCC ϭ emergency mass critical care T he severe acute respiratory syndrome epidemic of 2002-2003, recent natural disasters, burgeoning concern for intentional catastrophes, and the looming threat of a severe influenza pandemic have stimulated much recent debate about how to care for a surge of critically ill people. 1-12 Most countries, though, including those with widely available critical care services and investment in disaster preparedness, lack sufficient specialized staff, medical equipment, and ICU space to provide timely, usual critical care for a large influx of additional patients (see "Definitive Care for the Critically Ill During a Disaster: Current Capabilities and Limitations"). If a disaster yielded hundreds or thousands of critically ill
Output: Definitive Care for the Critically Ill During a Disaster: A Framework for Optimizing Critical Care Surge Capacity
Previous estimates of a generic level phylogeny for the ubiquitous parasitoid wasp subfamily Microgastrinae (Hymenoptera) have been problematic due to short internal branches deep in the phylogeny. These short branches might be attributed to a rapid radiation among the taxa, the use of genes that are unsuitable for the levels of divergence being examined, or insuYcient quantity of data. We added over 1200 nucleotides from four nuclear genes to a dataset derived from three genes to produce a dataset of over 3000 nucleotides per taxon. While the number of well-supported short branches in the phylogeny increased, we still did not obtain strong bootstrap support for every node. Parametric and nonparametric bootstrap simulations projected that an enormous, and likely unobtainable, amount of data would be required to get bootstrap support greater than 50% for every node. However, a marked increase in the number of well-supported nodes was seen when we conducted a Bayesian analysis of a combined dataset generated from morphological characters added to the seven gene dataset. Our results suggest that, in some cases, combining morphological and genetic characters may be the most practical way to increase support for short branches deep in a phylogeny.
Output: Dissecting the ancient rapid radiation of microgastrine wasp genera using additional nuclear genes
In ostriches, the population densities resulting from intensive rearing increases susceptibility to pathogens such as mycoplasmas. In addition to good management practices, vaccination offers an attractive alternative for controlling mycoplasma infections in food animals, instead of using antibiotics, which often leave unacceptable residues. The use of live attenuated vaccines, however, carry the concern of reversion to virulence or genetic recombination with field strains. Currently there are no commercially available vaccines against ostrich-infecting mycoplasmas and this study therefore set out to develop and evaluate the use of a DNA vaccine against mycoplasma infections in ostriches using an OppA protein as antigen. To this end, the oppA gene of "Mycoplasma nasistruthionis sp. nov." str. Ms03 was cloned into two DNA vaccine expression vectors after codon correction by site-directed mutagenesis. Three-months-old ostriches were then vaccinated intramuscularly at different doses followed by a booster vaccination after 6 weeks. The ability of the DNA vaccines to elicit an anti-OppA antibody response was evaluated by ELISA using the recombinant OppA protein of Ms03 as coating antigen. A statistically significant anti-OppA antibody response could be detected after administration of a booster vaccination indicating that the OppA protein was successfully immunogenic. The responses were also both dose and vector dependent. In conclusion, the DNA vaccines were able to elicit an immune response in ostriches and can therefore be viewed as an option for the development of vaccines against mycoplasma infections.
Output: DNA Vaccines Against Mycoplasma Elicit Humoral Immune Responses in Ostriches
The isolation of neutralizing monoclonal antibodies (nmAbs) against the Zika virus (ZIKV) might lead to novel preventative strategies for infections in at-risk individuals, primarily pregnant women. Here we describe the characterization of human mAbs from the plasmablasts of an acutely infected patient. One of the 18 mAbs had the unusual feature of binding to and neutralizing ZIKV despite not appearing to have been diversified by affinity maturation. This mAb neutralized ZIKV (Neut 50~2 μg/ml) but did not react with any of the four dengue virus serotypes. Except for the expected junctional diversity created by the joining of the V-(D)-J genes, there was no deviation from immunoglobulin germline genes. This is a rare example of a human mAb with neutralizing activity in the absence of detectable somatic hypermutation. Importantly, binding of this mAb to ZIKV was specifically inhibited by human plasma from ZIKV-exposed individuals, suggesting that it may be of value in a diagnostic setting.
Output: A human inferred germline antibody binds to an immunodominant epitope and neutralizes Zika virus
Background: Competitive interactions among bacteria in the respiratory tract microbiota influence which species can colonize and potentially contribute to pathogenesis of community-acquired pneumonia (CAP). However, understanding of the role of respiratory tract microbiota in the clinical course of pediatric CAP is limited. Methods: We sought to compare microbiota profiles in induced sputum and nasopharyngeal/oropharyngeal (NP/OP) samples from children and to identify microbiota profiles associated with CAP severity. We used 16S ribosomal RNA sequencing and several measures of microbiota profiles, including principal component analysis (PCA), to describe the respiratory microbiota in 383 children, 6 months to <18 years, hospitalized with CAP. We examined associations between induced sputum and NP/OP microbiota profiles and CAP severity (hospital length of stay and intensive care unit admission) using logistic regression. Results: Relative abundance of bacterial taxa differed in induced sputum and NP/OP samples. In children 6 months to < 5 years, the sputum PCA factor with high relative abundance of Actinomyces, Veillonella, Rothia, and Lactobacillales was associated with decreased odds of length of stay ≥ 4 days [adjusted odds ratio (aOR) 0.69; 95 % confidence interval (CI) 0.48-0.99]. The sputum factor with high relative abundance of Haemophilus and Pasteurellaceae was associated with increased odds of intensive care unit admission [aOR 1.52; 95 % CI 1.02-2.26]. In children 5 to < 18 years, the sputum factor with high relative abundance of Porphyromonadaceae, Bacteriodales, Lactobacillales, and Prevotella was associated with increased odds of length of stay ≥ 4 days [aOR 1.52; 95 % CI 1.02-2.26]. Taxa in NP/OP samples were not associated with CAP severity. Conclusion: Certain taxa in the respiratory microbiota, which were detected in induced sputum samples, are associated with the clinical course of CAP.
Output: Association of sputum microbiota profiles with severity of community-acquired pneumonia in children
Background: Acute viral respiratory infections (VRI) are the most common diseases in humans and are associated with high morbidity and mortality in infants and the elderly. Children with congenital heart disease (CHD) are more susceptible to get severe forms of VRI due to their altered lung mechanics, leading to several complications, such as increased hospital stay, longer mechanical ventilation, and higher mortality. This study aimed to identify the frequency of VRI in children with CHD undergoing cardiac surgery, and to compare the major outcomes according to the presence or absence of a VRI. Methods: This was a longitudinal, observational cohort study. Nasopharyngeal secretion samples were collected pre-and postoperatively for patients undergoing cardiac surgery, from May 2013 to May 2014. Respiratory viruses were detected using CLART Pneumovir®. Results: Forty-eight patients were enrolled. We found a VRI preoperatively in 16 children with CHD before surgery (33.3%), and the frequency of new infections was 8.3% (4 patients). However, in this study, in univariate analyses, the two groups did not differ in any of the studied outcomes. In the multivariate regression models, adjusting for age and STAT category, the presence of a VRI did not show a significant effect on the major outcomes. Conclusions: In conclusion, VRI was frequent in children undergoing open-heart surgery, but the presence of a VRI did not impact on major outcomes in this cohort.
Output: Epidemiology of viral respiratory infections in children undergoing heart surgery
Two multicentre surveys were conducted in France to estimate the prevalence of Cryptosporidium infection in calves using qualitative ELISA for detection of Cryptosporidium coproantigens and oocysts. The first survey involved 4-12-day-old calves in six dairy-calf distribution centres, collecting calves from seven Administrative Regions (Aquitaine, Bretagne, Franche-Comté, Lorraine, Normandie, Nord, Pays de Loire). For each region, 20 calves were selected every month for 12 consecutive months (October 1995-September 1996. Prevalence of Cryptosporidium infection was 17.9% (Confidence Intervals (C.I.) 95%=[16.1%; 19.8%]) among the 1628 selected calves, of which only 5.3% had diarrhoea. The second survey conducted between November 1995 and May 1996 involved 4-21-day-old calves examined by veterinary practitioners who selected 189 livestock farms of dairy-or suckler-type in ten Administrative Departments (Allier, Cantal, Creuse, Doubs, Ille-et-Vilaine, Maine-et-Loire, Manche, Pas-de-Calais, Saône-et-Loire, Vendée). Cryptosporidia were detected in 105 (55.6%) of the farms. Among the 440 calves examined, of which 398 (90.5%) presented diarrhoea, cryptosporidia were found in 191 animals, i.e. a prevalence of 43.4% (C.I. 95%=[38.8%; 48.0%]). Breed of calves and type of housing had very little impact on prevalence in this survey. Some regional variations could be noticed, even if cryptosporidia infection is widespread. Monthly variations could be related to seasonal peaks in calving with a lower infection rate during summer.
Output: Prevalence of Cryptosporidium infection in calves in France
Oral corticosteroids are the cornerstone of acute asthma management in the emergency department. Recent evidence has raised doubt about the efficacy of this treatment in preschool-aged children with viral-induced wheezing and in smoking adults. The aims of the study are to: (1) document the magnitude of response to oral corticosteroids in children presenting to the emergency department with moderate or severe asthma; (2) quantify potential determinants of response to corticosteroids, and (3) explore the role of gene polymorphisms associated with the responsiveness to corticosteroids The design is a prospective cohort study of 1008 children aged 1-17 years meeting a strict definition of asthma and presenting with a clinical score of ≥4 on the validated Pediatric Respiratory Assessment Measure (PRAM). All children will receive standardized severity-specific treatment with prednisone/prednisolone and co-interventions (salbutamol with/without ipratropium bromide). Determinants, namely viral aetiology, environmental tobacco smoke, and single nucleotide polymorphism will be objectively documented. The primary efficacy endpoint is hospital admission within 72 hours. Secondary endpoints include other measures of asthma severity and time to recovery within 7 days of the index visit. The study has 80% power for detecting a risk difference of 7.5% associated with each determinant from a baseline risk of 21%, at an α of 0.05. Ethical approval has been obtained from all participating institutions. An impaired response to systemic steroids in certain subgroups will challenge the current standard of practice and call for the immediate search for better approaches. A potential host-environment interaction will broaden our understanding
Output: Determinants Of Oral corticosteroid Responsiveness in Wheezing Asthmatic Youth (DOORWAY): protocol for a prospective multicentre cohort study of children with acute moderate-to-severe asthma exacerbations Determinants Of Oral corticosteroid Responsiveness in Wheezing Asthmatic Youth (DOORWAY): protocol for a prospective multicentre cohort study of children with acute moderate-to-severe asthma exacerbations
Data from all reported cases of 2009 pandemic influenza A (H1N1) were obtained from the China Information System for Disease Control and Prevention. The spatiotemporal distribution patterns of cases were characterized through spatial analysis. The impact of travel-related risk factors on invasion of the disease was analyzed using survival analysis, and climatic factors related to local transmission were identified using multilevel Poisson regression, both at the county level. The results showed that the epidemic spanned a large geographic area, with the most affected areas being in western China. Significant differences in incidence were found among age groups, with incidences peaking in school-age children. Overall, the epidemic spread from southeast to northwest. Proximity to airports and being intersected by national highways or freeways but not railways were variables associated with the presence of the disease in a county. Lower temperature and lower relative humidity were the climatic factors facilitating local transmission after correction for the effects of school summer vacation and public holidays, as well as population density and the density of medical facilities. These findings indicate that interventions focused on domestic travel, population density, and climatic factors could play a role in mitigating the public health impact of future influenza pandemics.
Output: Original Contribution Distribution and Risk Factors of 2009 Pandemic Influenza A (H1N1) in Mainland China
Infection control is an essential component of health care. The literature generally suggests that most health professionals' knowledge of infection control principles and standards is poor or, at the very least, inadequate. There is a paucity of research examining paramedic knowledge of infection control principles and standards, particularly in the Australian pre -hospital context. The purpose of this study was to determine paramedic knowledge of standard infection control definitions and principles in an Australian emergency medical system (EMS). A confidential and anonymous mail survey was distributed to all paramedics working in a State-wide Australian ambulance service (n=2274) A total of 1258 surveys were returned -a response rate of 55.3%. Only 46.2% (n=581) of the participants identified the correct components of the 'chain of infection'. Correct identification of the definition of 'nosocomial'was made by 27.9% (n=347) of participants. Less than onefifth (17.2%, n=217) of participants identified 'standards and additional precautions' as the current system of infection control. Less than half (41.6%, n=523) of the sample correctly identified hand washing as the primary infection control strategy to prevent cross-infection. This study suggests knowledge of fundamental principles and standards of infection control among paramedics is poor in this jurisdiction and recommends the introduction of comprehensive in-service education programmes in infection control. Further research is required to investigate if, and how, these results may be realised in practice.
Output: Paramedic knowledge of infection control principles and standards in an Australian emergency medical system (EMS)
Four types of porcine epidemic diarrhea virus (PEDV) variants with a large deletion in the spike protein were detected, together with the original US PEDV, from pig fecal and oral fluid samples collected during 2016-2017 in the US. Two of the variants are similar to those identified in Japan: one contains a 194-aa deletion, the same as PEDV variant TTR-2/ JPN/2014, while the other contains a 204-aa deletion, the same as PEDV variant JKa-292/CS1de204. Two new S1 NTDdel PEDV variants were found: one contains a 201-aa deletion located at residues 30-230 and the other contains a 202-aa deletion located at residues 24-225 of the S protein. This is the first report on coinfection of S1 NTD-del PEDV variants and the original US PEDV strain in US pigs, indicating that PEDV continues to evolve in pigs and might be responsible for disease pattern changes.
Output: New variants of porcine epidemic diarrhea virus with large deletions in the spike protein, identified in the United States, 2016-2017
Community-acquired pneumonia (CAP) remains one of the most common serious infections encountered among children worldwide. In this review, we highlight important literature and recent scientific discoveries that have contributed to our current understanding of pediatric CAP. We review the current epidemiology of childhood CAP in the developed world, appraise the state of diagnostic testing for etiology and prognosis, and discuss disease management and areas for future research in the context of recent national guidelines.
Output: Community-Acquired Pneumonia in the Conjugate Vaccine Era
This article aims to identify the epitope corresponding to SARS-CoV spike protein specific neutralizing monoclonal antibody (MAb) 2C5. The antibody was used as the target and three rounds of bio-panning were conducted with a phage-displayed peptide library. After the third panning, 20 phage-plaque clones were randomly picked and analyzed for the binding ability with the MAb 2C5 by ELISA. The displayed sequence analysis demonstrated that among the 20 phage clones, eight clones displayed the same seven-peptide TPEQQFT. All these eight phage-clones showed strongest binding activity with 2C5 in the phage ELISA analysis. Furthermore, phages displaying peptide TPEQQFT could specifically inhibit the binding of MAb 2C5 with SARS-CoV spike protein. The results demonstrated that TPEQQFT is a mimic epitope peptide containing neutralizing MAb 2C5. This study may provide information for further structural and functional analyses of spike protein and vaccine development for severe acute respiratory syndrome.
Output: Identification of a Mimotope Peptide Bound to the SARS-CoV Spike Protein Specific Monoclonal Antibody 2C5 with Phage-displayed Peptide Library
Background: There is indirect evidence that an increased infectious burden is associated with a decreased prevalence of IgE-mediated allergy during childhood. Objective: To determine whether there is a relation between the serostatus of 13 different viruses and parentally reported infections and IgE sensitization in 2-year-old children. To investigate whether there is an interaction between cytomegalovirus (CMV) and Epstein-Barr virus (EBV) in relation to IgE sensitization. Methods: A total of 246 infants were followed prospectively to 2 years of age with clinical examinations, skin prick test, and specific IgE analyses and through analysis of seropositivity against adenovirus, influenza, parainfluenza, respiratory syncytial virus, CMV, EBV, herpes simplex virus, human herpesvirus 6, and varicella-zoster virus. Results: There was some evidence that IgE sensitization (24%) tended to be more common among children who were seropositive against few compared with children who were seropositive against many viruses, but this was not statistically significant, and there was no consistent trend across the groups. IgE sensitization was statistically significantly less prevalent at 2 years of age among infants who were seropositive against EBV but not other viruses (adjusted odds ratio, 0.34; 95% CI, 0.14-0.86). The interaction of seropositivity against both CMV and EBV antibodies indicated a further reduction in the risk for IgE sensitization (adjusted odds ratio for interaction, 0.10; 95% CI, 0.01-0.92), indicating effect modification associated with seropositivity against CMV. Conclusion: Our results indicate that acquisition of EBV infection during the first 2 years of life is associated with a reduced risk of IgE sensitization, and this effect is enhanced by CMV coinfection. (J Allergy Clin Immunol 2005;116: 438-44.) 
Output: Does early EBV infection protect against IgE sensitization?
a b s t r a c t Three ionic liquids, [BMIM][BF 4 ] doped with 60 mol % of LiCl ([BMIM][BF 4 ]-LiCl), N,N,N,N-tetramethylguanidinium trifluoroacetate (TMGT), and N,N,N,N-tetramethylguanidinium triflate (TMGT f ) were found useful as catalyst solvents for controlled 3-indolylation of isatins. Our investigation revealed that the reaction between isatin and indoles in [BMIM] [BF 4 ]-LiCl or TMGT f media stops at the step of addition of the two components providing 3-indolyl-3-hydroxyindolin-2-ones while the ionic liquid TMGT runs the reaction further through accompanying Friedel-Crafts substitution to afford symmetrical 3,3-di(indol-3-yl)indolin-2-ones. To take advantage of the difference between the effects of these ionic liquids on the reaction progress, we planned a two-step protocol for the efficient synthesis of unsymmetrical 3,3-di(indol-3-yl)indolin-2-ones.
Output: Synthesis of symmetrical and unsymmetrical 3,3-di(indolyl)indolin-2-ones under controlled catalysis of ionic liquids
Background: Ribonucleic acid (RNA) molecules play important roles in many biological processes including gene expression and regulation. Their secondary structures are crucial for the RNA functionality, and the prediction of the secondary structures is widely studied. Our previous research shows that cutting long sequences into shorter chunks, predicting secondary structures of the chunks independently using thermodynamic methods, and reconstructing the entire secondary structure from the predicted chunk structures can yield better accuracy than predicting the secondary structure using the RNA sequence as a whole. The chunking, prediction, and reconstruction processes can use different methods and parameters, some of which produce more accurate predictions than others. In this paper, we study the prediction accuracy and efficiency of three different chunking methods using seven popular secondary structure prediction programs that apply to two datasets of RNA with known secondary structures, which include both pseudoknotted and non-pseudoknotted sequences, as well as a family of viral genome RNAs whose structures have not been predicted before. Our modularized MapReduce framework based on Hadoop allows us to study the problem in a parallel and robust environment. Results: On average, the maximum accuracy retention values are larger than one for our chunking methods and the seven prediction programs over 50 non-pseudoknotted sequences, meaning that the secondary structure predicted using chunking is more similar to the real structure than the secondary structure predicted by using the whole sequence. We observe similar results for the 23 pseudoknotted sequences, except for the NUPACK program using the centered chunking method. The performance analysis for 14 long RNA sequences from the Nodaviridae virus family outlines how the coarse-grained mapping of chunking and predictions in the MapReduce framework exhibits shorter turnaround times for short RNA sequences. However, as the lengths of the RNA sequences increase, the fine-grained mapping can surpass the coarse-grained mapping in performance. Conclusions: By using our MapReduce framework together with statistical analysis on the accuracy retention results, we observe how the inversion-based chunking methods can outperform predictions using the whole sequence. Our chunk-based approach also enables us to predict secondary structures for very long RNA sequences, which is not feasible with traditional methods alone. Figure 1 Basic elements in RNA secondary structures. The stem loop (a) and pseudoknot (b). Zhang et al. BMC Structural Biology 2013, 13(Suppl 1):S3
Output: Enhancement of accuracy and efficiency for RNA secondary structure prediction by sequence segmentation and MapReduce
From an aqueous decoction of the traditional Chinese medicine "ban lan gen" (the Isatis indigotica root), an antiviral natural product CI -39 was isolated as an NNRTI (non-nucleoside reverse transcriptase inhibitor) (EC 50 ¼ 3.40 mM). Its novel structure was determined as methyl (1-methoxy-1H-indol-3-yl) acetamidobenzoate by spectroscopic data and confirmed by single crystal X-ray diffraction. Through synthesis and structure-activity relationship (SAR) investigation of CI -39 and 57 new derivatives (24 with EC 50 values of 0.06e8.55 mM), two optimized derivatives 10f and 10i (EC 50 : 0.06 mM and 0.06 mM) having activity comparable to that of NVP (EC 50 ¼ 0.03 mM) were obtained. Further evaluation verified that 10f and 10i were RT DNA polymerase inhibitors and exhibited better activities and drug resistance folds compared to NVP against seven NNRTI-resistant strains carrying different mutations. Especially, 10i (EC 50 ¼ 0.43 mM) was more active to the L100I/K103N double-mutant strain as compared to both NVP (EC 50 ¼ 0.76 mM) and EFV (EC 50 ¼ 1.08 mM). The molecular docking demonstrated a possible binding pattern between 10i and RT and revealed activity mechanism of 10i against the NNRTI-resistant strains. a Chemical shift values (d) were measured at 500 MHz for 1 H and at 125 MHz for 13 C, respectively. Proton coupling constants (J) in Hz are given in parentheses. The assignments were based on DEPT, 1 He 1 H COSY, HSQC, and HMBC experiments. C. Xu et al.
Output: Discovery, synthesis, and optimization of an N-alkoxy indolylacetamide against HIV-1 carrying NNRTI-resistant mutations from the Isatis indigotica root
Rhinovirus (RV) role in pathogenesis of severe childhood disease remains controversial. We aimed to explore the association between RV molecular subtyping, nasopharyngeal viral loads and viremia with childhood pneumonia. Nasopharyngeal and blood samples from cases and controls were tested for RV and the 5′ non-coding region sequenced. The cases compared to controls had a similar prevalence of RV detection in the nasopharynx (23 % vs. 22 %, P = 0.66), similar RV species distribution (A, B, C = 44 %, 8%, 44 % vs. 48 %, 7%, 38 %; respectively; P = 0.66) and similar viral load (4.0 and 3.7 log10 copies/mL, P = 0.062). However, RV-viremia was 4.01-fold (aOR 95 % CI: 1.26-12.78) more prevalent among cases (7%) than controls (2%), P = 0.019. Furthermore, among cases and controls RV-C was more commonly associated with viremia (14 % and 4%, P = 0.023), than RV-A (2% and 1%; P = 0.529). Thus RV-viremia could be used as a measure for attributing causality to RV in children hospitalized for pneumonia.
Output: A prospective case-control study on the association of Rhinovirus nasopharyngeal viral load and viremia in South African children hospitalized with severe pneumonia
Although the SARS-CoV-2 viral load detection of respiratory specimen has been widely used for novel coronavirus disease diagnosis, it is undeniable that serum SARS-CoV-2 nucleic acid (RNAaemia) could be detected in a fraction of the COVID-19 patients. However, it is not clear that if the incidence of RNAaemia could be correlated with the occurrence of cytokine storm or with the specific class of patients. This study enrolled 48 patients with COVID-19 admitted to the General Hospital of Central Theater Command, PLA, a designated hospital in Wuhan, China. The patients were divided into three groups according to the Dia gnosis and Treatment of New Coronavirus Pneumonia (version 6) published by the National Health Commission of China. The clinical and laboratory data were collected. The serum viral load detection and serum IL-6 levels were determined. Except for routine statistical analysis, Generalized Linear Models (GLMs) analysis was used to establish a patient status prediction model based on real-time RT-PCR Ct value. The Result showed that cases with RNAaemia were exclusively confirmed in critically ill patients group and appeared to reflect the illness severity. Further more, the inflammatory cytokine IL-6 levels were significantly elevated in critically ill patients, which is almost 10-folds higher than those in other patients. More importantly, the extremely high IL-6 level was closely correlated with the incidence of RNAaemia (R=0.902) and the vital signs of COVID-19 patients (R= -0.682). Serum SARS-CoV-2 viral load (RNAaemia) is strongly associated with cytokine storm and can be used to predict the poor prognosis of COVID-19 patients. Moreover, our results strongly suggest that cytokine IL-6 should be considered as a therapeutic target in critically ill patients with excessive inflammatory response. All rights reserved. No reuse allowed without permission. the author/funder, who has granted medRxiv a license to display the preprint in perpetuity.
Output: Detectable serum SARS-CoV-2 viral load (RNAaemia) is closely associated with drastically elevated interleukin 6 (IL-6) level in critically ill COVID-19 patients
Elephant endotheliotropic herpesvirus-hemorrhagic disease (EEHV-HD) is the primary cause of acute, highly fatal, hemorrhagic diseases in young Asian elephants. Although monocytopenia is frequently observed in EEHV-HD cases, the role monocytes play in EEHV-disease pathogenesis is unknown. This study seeks to explain the responses of monocytes/macrophages in the pathogenesis of EEHV-HD. Samples of blood, frozen tissues, and formalin-fixed, paraffin-embedded (FFPE) tissues from EEHV1A-HD, EEHV4-HD, co-infected EEHV1A and 4-HD, and EEHV-negative calves were analyzed. Peripheral blood mononuclear cells (PBMCs) from the persistent EEHV4-infected and EEHV-negative calves were also studied. The results showed increased infiltration of Iba-1-positive macrophages in the inflamed tissues of the internal organs of elephant calves with EEHV-HD. In addition, cellular apoptosis also increased in the tissues of elephants with EEHV-HD, especially in the PBMCs, compared to the EEHV-negative control. In the PBMCs of persistent EEHV4-infected elephants, cytokine mRNA expression was high, particularly up-regulation of TNF-α and IFN-γ. Moreover, viral particles were observed in the cytoplasm of the persistent EEHV4-infected elephant monocytes. Our study demonstrated for the first time that apoptosis of the PBMCs increased in cases of EEHV-HD. Furthermore, this study showed that monocytes may serve as a vehicle for viral dissemination during EEHV infection in Asian elephants.
Output: Possible roles of monocytes/macrophages in response to elephant endotheliotropic herpesvirus (EEHV) infections in Asian elephants (Elephas maximus)
Several studies have shown a reduced efficacy of influenza vaccines in the elderly compared to young adults. In this study, we evaluated the immunogenicity and protective efficacy of a commercially available inactivated influenza vaccine (Fluzone 1 ) in young adult and aged mice. C57/BL6 mice were administered a single or double immunization of Fluzone 1 with or without CpG and challenged intranasally with H1N1 A/California/09 virus. A double immunization of Fluzone 1 adjuvanted with CpG elicited the highest level of protection in young adult mice which was associated with increases in influenza specific IgG, elevated HAI titres, reduced viral titres and lung inflammation. In contrast, the vaccine schedule which provided fully protective immunity in young adult mice conferred limited protection in aged mice. Antigen presenting cells from aged mice were found to be less responsive to in vitro stimulation by Fluzone and CpG which may partially explain this result. Our data are supportive of studies that have shown limited effectiveness of influenza vaccines in the elderly and provide important information relevant to the design of more immunogenic vaccines in this age group.
Output: CpG Improves Influenza Vaccine Efficacy in Young Adult but Not Aged Mice
The frequency, social, and economic impacts of natural disasters show exponential increases in recent decades. Cities and countries around the world have begun to realize that these events are no longer "hundred year" storms, but repeat within a few years. As urbanisation continues throughout this century, more and more people and more economic activity will be concentrated in at-risk areas; especially as new arrivals in cities throughout Asia and Africa are likely to be concentrated in the highest risk districts, much as they often are in North America and Europe today. This article reviews recent growth of natural disasters and considers how a systems approach can improve approaches to mitigation and adaptation of these risks and to recovery from such events.
Output: A systems approach to natural disaster resilience
Species: as yet not named cells may initiate another cycle of merogony resulting in four Type II infectious merozoites. In immunocompromised hosts, the asexual cycle may be persistent. Alternatively, merozoites from Type II meronts may initiate the sexual cycle of development. (4a) Microgametocytes produce 12 to 16 microgametes. (4b) Microgametes released from host cells seek out and fertilize macrogametocytes. (5) The resulting zygote differentiates into an oocyst (la) which is released into the intestinal lumen. (6) Thick-walled and thin-walled oocysts in varying stages of sporulation pass out of the host in feces. Thin-walled oocysts may spontaneously rupture in the host, ensuring persistent infection in immuno compromised hosts (arrow from 6 to 3a). (7) Oocyst released from a host of one mammalian species can infect a wide variety of mammals of other species. Young animals are most susceptible to infection. (Adapted with permission from Despommier and Karapelou, 1987.
Output: Cryptosporidiosis in Idaho lambs: Natural and experimental infections
Middle East Respiratory Syndrome Coronavirus (MERS-CoV) is an emerging zoonotic virus considered as one of the major public threat with a total number of 2 298 laboratory-confirmed cases and 811 associated deaths reported by World Health Organization as of January 2019. The transmission of the virus was expected to be from the camels found in Middle Eastern countries via the animal and human interaction. The genome structure provided information about the pathogenicity and associated virulent factors present in the virus. Recent studies suggested that there were limited insight available on the development of novel therapeutic strategies to induce immunity against the virus. The severities of MERS-CoV infection highlight the necessity of effective approaches for the development of various therapeutic remedies. Thus, the present review comprehensively and critically illustrates the recent aspects on the epidemiology of the virus, the structural and functional features of the viral genome, viral entry and transmission, major mechanisms of pathogenesis and associated virulent factors, current animal models, detection methods and novel strategies for the development of vaccines against MERS-CoV. The review further illustrates the molecular and computational virtual screening platforms which provide insights for the identification of putative drug targets and novel lead molecules toward the development of therapeutic remedies.
Output: Recent Aspects on the Pathogenesis Mechanism, Animal Models and Novel Therapeutic Interventions for Middle East Respiratory Syndrome Coronavirus Infections
Small and medium-sized tourism and hospitality enterprises (SMTHEs) are often susceptible to various hazards, which result in risk concerns. Insurance is recognised as one of the risk management strategies, but evidence indicates that insurance uptake among SMTHEs has been low. Yet, researchers have hardly researched into the factors that influence insurance uptake among SMTHEs. Two-hundred and fifty (250) respondents were selected using a multi-stage sampling technique. Confirmatory factor analysis, multivariate logit and probit regression techniques were used to determine factors underlying SMTHEs' insurance uptake. Risk concerns, the firm's characteristics, the perceived benefits of insurance and other informal risk coping mechanisms, as well as insurance service provision concerns were identified as determinants of insurance uptake. This is one of the first papers to offer a holistic understanding of the factors influencing SMTHEs' insurance subscription in a resourcescarce destination of Sub-Saharan Africa. The practical and theoretical implications of the paper are discussed.
Output: Tourism Management Perspectives Insurance uptake among small and medium-sized tourism and hospitality enterprises in a resource-scarce environment
Meaningfully synthesizing single case experimental data from intervention studies comprised of individuals with low incidence conditions and generating effect size estimates remains challenging. Seven effect size metrics were compared for single case design (SCD) data focused on teaching speech generating device use to individuals with intellectual and developmental disabilities (IDD) with moderate to profound levels of impairment. The effect size metrics included percent of data points exceeding the median (PEM), percent of nonoverlapping data (PND), improvement rate difference (IRD), percent of all nonoverlapping data (PAND), Phi, nonoverlap of all pairs (NAP), and Tau novlap . Results showed that among the seven effect size metrics, PAND, Phi, IRD, and PND were more effective in quantifying intervention effects for the data sample (N = 285 phase or condition contrasts). Results are discussed with respect to issues concerning extracting and calculating effect sizes, visual analysis, and SCD intervention research in IDD. effect size metric; speech generating devices; single case design; intellectual and developmental disabilities; evidence-based practices Evidence-based practice (EBP) has become a standard for an increasing number of educational and human services disciplines (American Speech-Language-Hearing domains of applied research, meta-analyses can be more challenging to implement because of the lack of agreed upon effect size metrics (Lipsey & Wilson, 2001; Shadish, Hedges, & Pustejovsky, 2014) . One area where this is particularly evident involves intervention research with low-incidence populations including individuals with intellectual and developmental disabilities (IDD) with moderate to profound levels of impairment. In the specific area of speech generating device (SGD) interventions for individuals with IDD with moderate to profound levels of impairment, for example, the population is extremely heterogeneous. This has resulted in a preponderance of single case design (SCD) studies for which there is not a standard effect size metric. In this article, we used the results from SCD SGD intervention studies as a vehicle to further evaluate different non-parametric effect size metrics from SCD studies. Our rationale was, in part, pragmatic. That is, the literature specific to SGD and severe disabilities is a manageable literature. Additionally, SGDs represent an area of a relatively rapid growth with tablet-based systems emerging and proliferating (Kuster, 2012; McNaughton & Light, 2013) . In the following sections we provide a brief overview of the literature addressing SGD and SCD. Subsequently, we provide a rationale for the SCD effect size comparisons that were conducted.
Output: Comparing Single Case Design Overlap-Based Effect Size Metrics From Studies Examining Speech Generating Device Interventions HHS Public Access The Need for Effect Size Clarity for Applied Intervention Research With Low-Incidence Populations Using SGDs