We know that we don't know: Children's understanding of common ignorance in a coordination game.

Common ground is the knowledge, beliefs, and suppositions shared between partners in an interaction. Previous research has focused extensively on what partners know they know together, that is, "common knowledge." However, another important aspect of common ground is what partners know they do not know together, that is, "common ignorance." A new coordination game was designed to investigate children's use of common ignorance. Without communicating or seeing each other's decisions, 4- to 8-year-olds needed to make the same decision as their partner about whether to try to retrieve a reward. To retrieve it, at least one of them needed to know a secret code. The knowledge/ignorance of both partners was ostensively manipulated by showing one partner, both partners, or neither partner the secret code in four conditions: common knowledge (both knew the code), common ignorance (neither partner knew the code), common privileged self knowledge (only children knew the code), and common privileged other knowledge (only their partner knew the code). Children's decisions, latency, and uncertainty were coded. Results showed that the common ignorance states were generally more difficult than the common knowledge states. Unexpectedly, children at all ages had difficulty with coordinating when their partner knew the code but they themselves did not (common privileged other knowledge). This study shows that, along with common knowledge, common ignorance and common privileged self knowledge and other knowledge also play important roles in coordinating with others but may develop differently.

A Randomized, Double-Blind, Placebo-Controlled, Parallel-Group Phase 2b Trial of P2X3 Receptor Antagonist Sivopixant for Refractory or Unexplained Chronic Cough.

INTRODUCTION: To determine the optimal dose of sivopixant, a highly selective P2X3 receptor antagonist, for refractory or unexplained chronic cough (RCC/UCC). METHODS: In this phase 2b, randomized, double-blind, placebo-controlled, parallel-group, multicenter trial, patients received sivopixant 50, 150, or 300 mg or placebo once daily for 4 weeks. The primary endpoint was a change from baseline in 24-h cough frequency (coughs/h) with sivopixant vs placebo. RESULTS: Overall, 390/406 randomized patients completed the study. Placebo-adjusted changes in hourly cough count over 24 h were 13.17% (P = 0.3532), - 1.77% (P = 0.8935), and - 12.47% (P = 0.3241) and in cough severity (visual analog scale) were 1.75 mm (P = 0.5854), - 1.21 mm (P = 0.7056), and - 6.55 mm (P = 0.0433) with sivopixant 50, 150, and 300 mg, respectively. Placebo-adjusted changes from baseline in Leicester Cough Questionnaire total scores were - 0.37 (P = 0.4207), - 0.07 (P = 0.8806), and 0.69 (P = 0.1473) with sivopixant 50, 150, and 300 mg, respectively. Additionally, 61.3%, 78.3%, 86.8%, and 71.4% of patients receiving sivopixant 50, 150, and 300 mg and placebo, respectively, reported any improvements in Patient Global Impression of Change. The incidence of treatment-emergent adverse events (TEAEs) was 25.7%, 32.0%, 49.0%, and 20.6% in sivopixant 50, 150, and 300 mg and placebo groups, respectively; all TEAEs in the sivopixant group were mild-to-moderate. CONCLUSION: Sivopixant did not demonstrate a statistically significant difference vs placebo in change from baseline in 24-h cough frequency. The dose of 300 mg has potential for RCC/UCC, showing the greatest improvements in cough frequency and patient-reported outcomes and dose-related mild to moderate reversible taste disturbance, although further trials are needed. CLINICAL TRIAL REGISTRATION: ClinicalTrials.gov identifier NCT04110054; registered September 26, 2019.

Evaluating the Effect of a Telepsychiatry Educational Program on the Awareness, Knowledge, Attitude, and Skills of Telepsychiatry Among Spanish Psychiatrists during COVID-19 Pandemic.

Introduction: The COVID-19 pandemic has renewed the interest in telepsychiatry as a way to help psychiatrists care for their patients, but mental health providers' unfamiliarity and concerns may impede implementation of such services. This study aimed to determine the effect of an online educational intervention on awareness, knowledge, attitude, and skills (AKAS) of telepsychiatry among psychiatrists. Methods: The study used a pre-post-test design to compare AKAS of telepsychiatry among psychiatrists participating in an online course of practical telepsychiatry. The telemedicine AKAS questionnaire adapted to telepsychiatry was applied before and after the educational intervention, during the months of October to December 2020. Results: Responses from 213 participants were analyzed before the educational intervention and from 152 after it. The knowledge showed by Spanish psychiatrists before the educational intervention was good in 61% of participants, fair in 37%, and inadequate in 2%. With respect to attitudes toward telepsychiatry, 62% self-reported a high attitude, 33% moderate, and 5% low. With regard self-reported skills, 57% of the participating psychiatrists were highly skilled or experts, 22% moderately skilled, and 9% unskilled in handling telepsychiatry equipment. Despite the high baseline values, the educational intervention significantly improved psychiatrists' awareness, knowledge and attitudes toward telepsychiatry although not their skills. Conclusions: Online course of practical telepsychiatry was effective although future editions need to improve its focus on skills. This educational intervention represents an effort to promote the implementation of telepsychiatry as a health care alternative.

RNA structure-altering mutations underlying positive selection on Spike protein reveal novel putative signatures to trace crossing host-species barriers in Betacoronavirus.

Similar to other RNA viruses, the emergence of Betacoronavirus relies on cross-species viral transmission, which requires careful health surveillance monitoring of protein-coding information as well as genome-wide analysis. Although the evolutionary jump from natural reservoirs to humans may be mainly traced-back by studying the effect that hotspot mutations have on viral proteins, it is largely unexplored if other impacts might emerge on the structured RNA genome of Betacoronavirus. In this survey, the protein-coding and viral genome architecture were simultaneously studied to uncover novel insights into cross-species horizontal transmission events. We analysed 1,252,952 viral genomes of SARS-CoV, MERS-CoV, and SARS-CoV-2 distributed across the world in bats, intermediate animals, and humans to build a new landscape of changes in the RNA viral genome. Phylogenetic analyses suggest that bat viruses are the most closely related to the time of most recent common ancestor of Betacoronavirus, and missense mutations in viral proteins, mainly in the S protein S1 subunit: SARS-CoV (G > T; A577S); MERS-CoV (C > T; S746R and C > T; N762A); and SARS-CoV-2 (A > G; D614G) appear to have driven viral diversification. We also found that codon sites under positive selection on S protein overlap with non-compensatory mutations that disrupt secondary RNA structures in the RNA genome complement. These findings provide pivotal factors that might be underlying the eventual jumping the species barrier from bats to intermediate hosts. Lastly, we discovered that nearly half of the Betacoronavirus genomes carry highly conserved RNA structures, and more than 90% of these RNA structures show negative selection signals, suggesting essential functions in the biology of Betacoronavirus that have not been investigated to date. Further research is needed on negatively selected RNA structures to scan for emerging functions like the potential of coding virus-derived small RNAs and to develop new candidate antiviral therapeutic strategies.

Applicability of inter-primer binding site iPBS- retrotransposon marker system for the assessment of genetic diversity and population structure of Peruvian rosewood (Aniba rosaeodora Ducke) germplasm.

BACKGROUND: Rosewood (Aniba rosaeodora Ducke), which has a great demand due to its essential oil globally, is an evergreen tree of the Amazon forests. Rosewood natural stands have been depleted through deforestation and the destruction of habitat. Currently, rosewood is included in the ICUN red list of endangered species. METHODS AND RESULTS: The 11 highly polymorphic primers amplified total 305 bands of which 301 (98.69%) were polymorphic. The number of effective alleles (Ne), Shannon's information index (I), overall gene diversity (Ht), gene diversity (h), and polymorphism information content (PIC) were (1.562), (0.505), (0.330), (0.337) and (0.343), respectively. These diversity indices explored high genetic diversity in rosewood germplasm. Among studied germplasm, the Santa Marta population was found most diverse by reflecting higher values of diversity indices while the Zungarococha population was found least diverse. The analysis of molecular variance (AMOVA) revealed that 79% of the genetic variation was within the populations. The STRUCTURE algorithm, unweighted pair group with arithmetic mean (UPGMA), and principal coordinate's analysis (PCoA) separated all germplasms into different population groups according to their geographic locations. Santa Marta population was found more diverse by reflecting higher values of diversity indices. The maximum genetic distance (0.868) was found between the Huajoya-10 and Nanay-3. In this investigation, iPBS- retrotransposon marker system was used to explore the genetic diversity of Peruvian rosewood germplasm. CONCLUSIONS: The results in this study such as higher genetic diversity indices, AMOVA (79%) within population and PIC value (0.343) showed the utility and reproducibility of iPBS-retrotransposons in this species successfully. The STRUCTURE algorithm separated the germplasms into six population groups according to their geographic locations. These results have valuable information for the conservation, management strategies and future breeding activities of rosewood.

Glycogen synthase kinase 3ß participates in late stages of Dengue virus-2 infection.

BACKGROUND: Viruses can modulate intracellular signalling pathways to complete their infectious cycle. Among these, the PI3K/Akt pathway allows prolonged survival of infected cells that favours viral replication. GSK3ß, a protein kinase downstream of PI3K/Akt, gets inactivated upon activation of the PI3K/Akt pathway, and its association with viral infections has been recently established. In this study, the role of GSK3ß during Dengue virus-2 (DENV-2) infection was investigated. METHODS: GSK3ß participation in the DENV-2 replication process was evaluated with pharmacological and genetic inhibition during early [0-12 h post-infection (hpi)], late (12-24 hpi), and 24 hpi in Huh7 and Vero cells. We assessed the viral and cellular processes by calculating the viral titre in the supernatants, In-Cell Western, western blotting and fluorescence microscopy. RESULTS: Phosphorylation of GSK3ß-Ser9 was observed at the early stages of infection; neither did treatment with small molecule inhibitors nor pre-treatment prior to viral infection of GSK3ß reduce viral titres of the supernatant at these time points. However, a decrease in viral titres was observed in cells infected and treated with the inhibitors much later during viral infection. Consistently, the infected cells at this stage displayed plasma membrane damage. Nonetheless, these effects were not elicited with the use of genetic inhibitors of GSK3ß. CONCLUSIONS: The results suggest that GSK3ß participates at the late stages of the DENV replication cycle, where viral activation may promote apoptosis and release of viral particles.

A gestural repertoire of 1- to 2-year-old human children: in search of the ape gestures.

When we compare human gestures to those of other apes, it looks at first like there is nothing much to compare at all. In adult humans, gestures are thought to be a window into the thought processes accompanying language, and sign languages are equal to spoken language with all of its features. Some research firmly emphasises the differences between human gestures and those of other apes; however, the question about whether there are any commonalities is rarely investigated, and has mostly been confined to pointing gestures. The gestural repertoires of nonhuman ape species have been carefully studied and described with regard to their form and function-but similar approaches are much rarer in the study of human gestures. This paper applies the methodology commonly used in the study of nonhuman ape gestures to the gestural communication of human children in their second year of life. We recorded (n = 13) children's gestures in a natural setting with peers and caregivers in Germany and Uganda. Children employed 52 distinct gestures, 46 (89%) of which are present in the chimpanzee repertoire. Like chimpanzees, they used them both singly, and in sequences, and employed individual gestures flexibly towards different goals.

Contrast and Homogeneity Feature Analysis for Classifying Tremor Levels in Parkinson's Disease Patients.

Early detection of different levels of tremors helps to obtain a more accurate diagnosis of Parkinson's disease and to increase the therapy options for a better quality of life for patients. This work proposes a non-invasive strategy to measure the severity of tremors with the aim of diagnosing one of the first three levels of Parkinson's disease by the Unified Parkinson's Disease Rating Scale (UPDRS). A tremor being an involuntary motion that mainly appears in the hands; the dataset is acquired using a leap motion controller that measures 3D coordinates of each finger and the palmar region. Texture features are computed using sum and difference of histograms (SDH) to characterize the dataset, varying the window size; however, only the most fundamental elements are used in the classification stage. A machine learning classifier provides the final classification results of the tremor level. The effectiveness of our approach is obtained by a set of performance metrics, which are also used to show a comparison between different proposed designs.

Developmental changes in the influence of conventional and instrumental cues on over-imitation in 3- to 6-year-old children.

Previous studies have shown that children in the preschool period are fastidious imitators who copy models with such high levels of fidelity that task efficiency may be compromised. This over-imitative tendency, and the pervasive nature of it, has led to many explorations and theoretical interpretations of this behavior, including social, causal, and conventional explanations. In support of the conventional account, recent research has shown that children are more likely to over-imitate when the task is framed using conventional verbal cues than when it is framed using instrumental verbal cues. The aim of the current study was to determine whether 3- to 6-year-old children (N=185, mean age=60 months) would over-imitate when presented with instrumental and conventional verbal cues, which varied only minimally and were more directly comparable between instrumental and conventional contexts than those used in previous studies. In addition to varying the overall context, we also varied the instrumental prompt used such that the cues provided ranged in the extent to which they provided explicit instruction to omit the irrelevant actions. Counter to our predictions, and the high levels of over-imitation witnessed in previous studies, the older children frequently over-imitated irrespective of the context provided, whereas the youngest children over-imitated selectively, including the irrelevant actions only when the task was presented in a conventional frame. We propose that the age differences found following an instrumental presentation are a result of the youngest children being more open to the motivation of learning the causality of the task, whereas the older children were more strongly motivated to adopt a social convention.

Molecular detection of flaviviruses and alphaviruses in mosquitoes (Diptera: Culicidae) from coastal ecosystems in the Colombian Caribbean.

Arboviruses belonging to the genera Flavivirus and Alphavirus were detected in mosquitoes in a rural area of San Bernardo del Viento (Córdoba, Colombia). A total of 22,180 mosquitoes were collected, sorted into 2,102 pools, and tested by generic/nested reverse transcription-polymerase chain reaction. Venezuelan equine encephalitis virus, dengue virus, West Nile virus, St. Louis encephalitis virus, yellow fever virus, and Culex flavivirus were detected and identified by sequencing. The detection of arboviral pathogens in this zone represents possible circulation and indicates a human health risk, demonstrating the importance of virological surveillance activities.

Evolutionary relationships of West Nile virus detected in mosquitoes from a migratory bird zone of Colombian Caribbean.

BACKGROUND: West Nile virus (WNV) is a member of the genus Flavivirus, and it is transmitted between Culex sp. mosquitoes and avian hosts. Equids and humans are commonly infected with WNV as dead-end hosts, and the signs and symptoms of infection range from mild illness to neurologic symptoms as encephalitis, meningitis and sometimes death. Previous phylogenetic studies have classified WNV into six genetically distinct lineages and provided valuable insight on WNV dispersal patterns within the Americas and its emergence in different geographic areas. In this study, we isolated, sequenced and genetically characterized the NS5 and envelope genes for two WNV strains detected from Northern of Colombia. Herein we describe the evolutionary relationships with representative WNV-strains isolated in a variety of epidemic outbreaks and countries, to define the phylogeographic origin and possible implications in the epidemiology of this emergent virus in Colombia. FINDINGS: Fragments of the NS5 and Envelope genes were amplified with RT-PCR and sequenced to obtain 1186-nt and 1504-nt portions, respectively. Our sequences were aligned with 46 sequences from WNV-strains collected in the U.S., Mexico and Argentina for phylogenetic reconstruction using Bayesian methods. Sequence analyses identified unique non-synonymous substitutions in the envelope gene of the WNV strains we detected, and our sequences clustered together with those from the attenuated Texas - 2002 genotype. CONCLUSIONS: A new strain closely related to attenuated strains collected in Texas during 2002 was identified from Colombia by phylogenetic analysis. This finding may explain the absence of human/equine cases of WNV-encephalitis or severe disease in Colombia and possibly other regions of South America. Follow-up studies are needed in ecosystems used by migratory birds areas and virological/entomological surveillance.

Gorillas with white sclera: A naturally occurring variation in a morphological trait linked to social cognitive functions.

Human eye morphology is considered unique among the primates in that humans possess larger width/height ratios (WHR), expose a greater amount of visible sclera (SSI; width of exposed eyeball/width of visible iris), and critically, have a white sclera due to a lack of pigmentation. White sclera in humans amplifies gaze direction, whereas the all-dark eyes of apes are hypothesized to conceal gaze from others. This study examines WHR and SSI in humans (N = 13) and gorillas (N = 85) engaged in direct and averted gazes and introduces a qualitative assessment of sclera color to evaluate variations in sclera pigmentation. The results confirm previous findings that humans possess a larger WHR than gorillas but indicate that humans and gorillas display similar amounts of visible sclera. Additionally, 72% (N = 124) of gorilla eyes in this sample deviated from the assumed all-dark eye condition. This questions whether gaze camouflage is the primary function of darkened sclera in non-human primates or whether other functional roles can be ascribed to the sclera, light or dark. We argue that white sclera evolved to amplify direct gazes in humans, which would have played a significant role in the development of ostensive communication, which is communication that both shows something and shows the intention to show something. We conclude that the horizontal elongation of the human eye, rather than sclera color, more reliably distinguishes human from great ape eyes, represented here by gorillas.

Molecular identification of Saint Louis encephalitis virus genotype IV in Colombia.

Saint Louis encephalitis virus (SLEV) is a member of the Japanese-encephalitis virus serocomplex of the genus Flavivirus. SLEV is broadly distributed in the Americas and the Caribbean Islands, where it is usually transmitted by mosquitoes of the genus Culex and primarily to birds and mammalian-hosts. Humans are occasionally infected by the virus and are dead-end hosts. SLEV causes encephalitis in temperate regions, while in tropical regions of the Americas, several human cases and a wide biological diversity of SLEV-strains have been reported. The phylogenetic analysis of the envelope (E) protein genes indicated eight-genotypes of SLEV with geographic overlap. The present paper describes the genotyping of two SLEV viruses detected in mosquito-pools collected in northern Colombia (department of Cordoba). We used reverse transcription-polymerase chain reaction to amplify a fragment of the E-gene to confirm the virus identity and complete E-gene sequencing for phylogenetic analysis and genotyping of the two-SLEV viruses found circulating in Córdoba. This is the first report of SLEV genotype IV in Colombia (Córdoba) in mosquitoes from a region of human inhabitation, implicating the risk of human disease due to SLEV infection. Physicians should consider SLEV as a possible aetiology for undiagnosed febrile and neurologic syndromes among their patients who report exposure to mosquito-bites.

A Double-Blind, Placebo-Controlled Comparator Study of LY2140023 monohydrate in patients with schizophrenia.

BACKGROUND: Pomaglumetad methionil (LY2140023 monohydrate) is a potent and highly selective agonist for the metabotropic glutamate mGluR2 and mGluR3 receptors. We present results of a pivotal clinical study H8Y-MC-HBBM assessing the efficacy of LY2140023 in improving symptoms as a monotherapy in patients with an acute exacerbation of schizophrenia. METHODS: Enrolled adult patients (ages 18-65) with schizophrenia who had experienced an exacerbation of symptoms within 2 weeks prior to study entry. Patients (N = 1013) were randomized 2:2:2:1 to treatment with placebo, LY40 mg twice daily (BID), LY80 mg BID, or risperidone (RIS) 2 mg BID for 6 weeks after a one-week blinded placebo lead-in. The primary outcome assessed change from baseline in the Positive and Negative Syndrome Scale (PANSS) total score in an overall schizophrenia population and a predefined subpopulation which excluded non-Hispanic white patients with the A/A genotype at the HTR2A SNP rs7330461. RESULTS: Neither LY2140023 dose showed significant improvement compared to placebo on PANSS total in either population (1-sided p-value [significance level], overall: LY40, p = .154 [0.01]; LY80, p = .698 [0.01], subpopulation: LY40, p = .033 [0.0025]; LY80, p = .659 [0.0025], MMRM analysis). RIS statistically separated from placebo in both populations (p < .001 [0.05]). There were no statistically significant differences in the incidence of serious adverse events, and no seizures on LY2140023. CONCLUSION: LY2140023 treatment did not demonstrate efficacy in populations studied. Overall, LY2140023 treatment was generally well tolerated with no new adverse safety findings compared to previous trials. Further understanding of the role of glutamate as a therapeutic target in schizophrenia is needed. CLINICAL TRIALS REGISTRATION: A Phase 2, Multicenter, Double-Blind, Placebo-Controlled Comparator Study of 2 Doses of LY2140023 Versus Placebo in Patients With DSM-IV-TR SchizophreniaClinicalTrials.gov identifier: NCT01086748.

Safety and efficacy of olanzapine in the long-term treatment of Japanese patients with bipolar I disorder, depression: an integrated analysis.

AIM: Safety and efficacy of long-term olanzapine treatment in Japanese patients with bipolar depression were assessed. METHODS: An integrated analysis of data from two studies was performed in olanzapine-treated patients (n = 165) with bipolar depression. Study 1 was a 6-week, double-blind, global study. Patients were randomly assigned to olanzapine or placebo followed by 18 weeks of open-label treatment. Study 2 was an open-label extension of Study 1 involving only Japanese patients. Patients assigned to Pre-olanzapine and Pre-placebo in Study 1 were treated for 24 weeks (total olanzapine exposure 42 or 48 weeks) and newly recruited patients (New-olanzapine) were treated for 48 weeks. Safety outcomes included treatment-emergent adverse events and changes in metabolic parameters. Efficacy outcome was assessed with Montgomery-Åsberg Depression Rating Scale score. RESULTS: Forty-three percent of patients completed the 42- or 48-week olanzapine treatment period. The most common treatment-emergent adverse event was weight increased (47.9%). Significant increases were seen in weight (3.5 kg), and in fasting glucose (3.5 mg/dL), fasting total cholesterol (8.1 mg/dL), and fasting triglycerides (35.1 mg/dL). Remission rates (Montgomery-Åsberg Depression Rating Scale total score ≤12 at any time) were 79.8% for the Pre-olanzapine group, 90.2% for the Pre-placebo group, and 85.0% for the New-olanzapine group. No patents developed mania during treatment. CONCLUSIONS: Long-term use of olanzapine in a Japanese population with bipolar depression is associated with increases in weight and fasting metabolic measures, and also with improved depressive symptoms with avoidance of mania. Clinicians must carefully consider the benefits and risks of long-term therapy with olanzapine.

Toward a Categorization of Virus-ncRNA Interactions in the World of RNA to Disentangle the Tiny Secrets of Dengue Virus.

In recent years, the function of noncoding RNAs (ncRNAs) as regulatory molecules of cell physiology has begun to be better understood. Advances in viral molecular biology have shown that host ncRNAs, cellular factors, and virus-derived ncRNAs and their interplay are strongly disturbed during viral infections. Nevertheless, the folding of RNA virus genomes has also been identified as a critical factor in regulating canonical and non-canonical functions. Due to the influence of host ncRNAs and the structure of RNA viral genomes, complex molecular and cellular processes in infections are modulated. We propose three main categories to organize the current information about RNA-RNA interactions in some well-known human viruses. The first category shows examples of host ncRNAs associated with the immune response triggered in viral infections. Even though miRNAs introduce a standpoint, they are briefly presented to keep researchers moving forward in uncovering other RNAs. The second category outlines interactions between virus-host ncRNAs, while the third describes how the structure of the RNA viral genome serves as a scaffold for processing virus-derived RNAs. Our grouping may provide a comprehensive framework to classify ncRNA-host-cell interactions for emerging viruses and diseases. In this sense, we introduced them to organize DENV-host-cell interactions.

Selection of software agile practices using Analytic hierarchy process.

Context: The increasing use of software and information technology in modern society requires that the deployment of IT solutions should be more efficient and controlled. In this sense, agile methodologies are essential to achieve this goal, but a relevant question arises: Which is the right methodology for reaching that goal? Objective: The purpose of the research was to study the prioritization of agile practices and improvement objectives in the context of software development, using the Analytic Hierarchy Process (AHP) method. For this purpose, 42 agile practices, 16 improvement objectives, 4 organizations dedicated to software development in Colombia and 40 professionals in the area of information and communication technologies in the same country were considered. Method: ology: The methodological approach used was mixed. On the one hand, we applied a quantitative approach for the treatment of data with the AHP method and, on the other hand, a qualitative analysis by consulting experts through a digital survey to validate the prioritization of the improvement objectives. Questionpro was used as a support tool for multicriteria comparison. Results: The main results show that applying AHP allowed us to prioritize 6 improvement objectives and 5 agile practices, where it is highlighted that the prioritization does not discard the other objects of comparison but allows us to put into practice the prioritized elements to favor their progressive implementation. The non-prioritized elements could be part of future iterations of multicriteria comparison that go hand in hand with capacity development and organizational maturity models in the context of global software development. Conclusion: It is highlighted that, although there is evidence of the application of multi-criteria comparison methods in the software development industry, this work applies such methods in the context of four different agile methodologies, which translates into a precedent for the conformation of hybrid methodological approaches.

Systematic computational hunting for small RNAs derived from ncRNAs during dengue virus infection in endothelial HMEC-1 cells.

In recent years, a population of small RNA fragments derived from non-coding RNAs (sfd-RNAs) has gained significant interest due to its functional and structural resemblance to miRNAs, adding another level of complexity to our comprehension of small-RNA-mediated gene regulation. Despite this, scientists need more tools to test the differential expression of sfd-RNAs since the current methods to detect miRNAs may not be directly applied to them. The primary reasons are the lack of accurate small RNA and ncRNA annotation, the multi-mapping read (MMR) placement, and the multicopy nature of ncRNAs in the human genome. To solve these issues, a methodology that allows the detection of differentially expressed sfd-RNAs, including canonical miRNAs, by using an integrated copy-number-corrected ncRNA annotation was implemented. This approach was coupled with sixteen different computational strategies composed of combinations of four aligners and four normalization methods to provide a rank-order of prediction for each differentially expressed sfd-RNA. By systematically addressing the three main problems, we could detect differentially expressed miRNAs and sfd-RNAs in dengue virus-infected human dermal microvascular endothelial cells. Although more biological evaluations are required, two molecular targets of the hsa-mir-103a and hsa-mir-494 (CDK5 and PI3/AKT) appear relevant for dengue virus (DENV) infections. Here, we performed a comprehensive annotation and differential expression analysis, which can be applied in other studies addressing the role of small fragment RNA populations derived from ncRNAs in virus infection.

A predator-prey fractional model with disease in the prey species.

In this paper, we study a generalized eco-epidemiological model of fractional order for the predator-prey type in the presence of an infectious disease in the prey. The proposed model considers that the disease infects the prey, causing them to be divided into two classes, susceptible prey and infected prey, with different density-dependent predation rates between the two classes. We propose logistic growth in both the prey and predator populations, and we also propose that the predators have alternative food sources (i.e., they do not feed exclusively on these prey). The model is evaluated from the perspective of the global and local generalized derivatives by using the generalized Caputo derivative and the generalized conformable derivative. The existence, uniqueness, non-negativity, and boundedness of the solutions of fractional order systems are demonstrated for the classical Caputo derivative. In addition, we study the stability of the equilibrium points of the model and the asymptotic behavior of its solution by using the Routh-Hurwitz stability criteria and the Matignon condition. Numerical simulations of the system are presented for both approaches (the classical Caputo derivative and the conformable Khalil derivative), and the results are compared with those obtained from the model with integro-differential equations. Finally, it is shown numerically that the introduction of a predator population in a susceptible-infectious system can help to control the spread of an infectious disease in the susceptible and infected prey population.

A randomized, double-blind, placebo-controlled study of rapid-acting intramuscular olanzapine in Japanese patients for schizophrenia with acute agitation.

BACKGROUND: Olanzapine rapid-acting intramuscular (IM) injection is an atypical antipsychotic drug already used overseas and recently approved in Japan. The objective of this study was to confirm the efficacy of rapid-acting IM olanzapine 10 mg was greater than IM placebo in patients with exacerbation of schizophrenia with acute psychotic agitation by comparing changes from baseline to 2 hours after the first IM injection, as measured by the Positive and Negative Syndrome Scale-Excited Component (PANSS-EC) total score. METHODS: We conducted a placebo-controlled, randomized, double-blind, parallel-group study in Japanese patients diagnosed with schizophrenia according to the diagnostic criteria specified in the DSM-IV-TR. Patients were randomized to 2 treatment groups: IM olanzapine (10 mg) or IM placebo. The primary efficacy outcome was the change in PANSS-EC from baseline to 2 hours after the first IM injection. Treatment groups were compared with an analysis of variance model which included treatment and site as factors. During the 24-hour treatment period, safety was assessed by clinical examination and laboratory investigations, electrocardiograms, extrapyramidal symptoms scales, and recording spontaneously reported adverse events. RESULTS: Of the 91 randomized patients, 90 patients (45 IM olanzapine-group; 45 IM placebo-group) were in the full analysis set. The mean change of PANSS-EC total score from baseline to 2 hours after the first IM injection (mean±standard deviation) was -9.2±4.5 for the IM olanzapine group and -2.8±5.6 for the IM placebo group. The difference between treatment groups was statistically significant (p<.001). There were no deaths, serious adverse events, treatment-emergent adverse events (TEAEs) leading to discontinuation, severe TEAEs, or instances of oversedation in this study. There were no statistically significant differences between treatment groups in the proportion of patients with potentially clinically significant changes in laboratory tests, vital signs (blood pressure and pulse rate), electrocardiograms, and treatment-emergent extrapyramidal symptoms. CONCLUSION: The efficacy of IM olanzapine 10 mg in patients with exacerbation of schizophrenia with acute psychotic agitation was greater than IM placebo in the primary efficacy measure, PANSS-EC. Intramuscular olanzapine 10 mg was shown to be generally safe and tolerable, and could be a new option for treatment of schizophrenia in Japan. TRIAL REGISTRATION: NCT00970281.