Expect the unexpected.
Ontology highlight
ABSTRACT:
SUBMITTER: Blaise D
PROVIDER: S-EPMC8351886 | biostudies-literature | 2021 Jun
REPOSITORIES: biostudies-literature
Publications
Similar Datasets
Project description:Hepatitis C virus (HCV) is continuing to spread worldwide, adding three million new infections each year. Currently approved therapies are highly effective; however, access to them is limited due to the high cost of treatment. Therefore, a cost effective vaccine and alternative antivirals remain essential. HCV envelope glycoproteins, E1 and E2, heterodimerize on the virion surface and are the major determinant for virus pathogenicity and host immune response. Recent structural insights into amino-terminal domain of E1 and core of E2 have revealed unexpected folds not present in glycoproteins from related viruses. Here we discuss these structural findings with respect to their role in HCV entry and impact on potential vaccine design and new antivirals.
| S-EPMC4505365 | biostudies-literature
Project description:Emerging virus diseases are a major threat to human and veterinary public health. With new examples occurring approximately one each year, the majority are viruses originating from an animal host. Of the many factors responsible, changes to local ecosystems that perturb the balance between pathogen and principal host species is one of the major drivers, together with increasing urbanization of mankind and changes in human behavior. Many emerging viruses have RNA genomes and as such are capable of rapid mutation and selection of new variants in the face of environmental changes in host numbers and available target species. This review summarizes recent work on aspects of virus emergence and the current understanding of the molecular and immunological basis whereby viruses may cross between species and become established in new ecological niches. Emergence is hard to predict, although mathematical modeling and spatial epidemiology have done much to improve the prediction of where emergence may occur. However, much needs to be done to ensure adequate surveillance is maintained of animal species known to present the greatest risk thus increasing general alertness among physicians, veterinarians and those responsible for formulating public health policy.
| S-EPMC3630908 | biostudies-other
Project description:BRCA1/2 pathogenic variants are widely known as major risk factors mainly for breast and ovarian cancer, while their role in gastrointestinal (GI) malignancies such as colorectal cancer (CRC), gastric cancer and oesophageal cancer (OeC) is still not well established. The main objective of this review is to summarise the available evidence on this matter. The studies included in the review were selected from PubMed/GoogleScholar/ScienceDirect databases to identify published articles where BRCA1/2 pathogenic variants were assessed either as a risk factor or a prognostic/predictive factor in these malignancies. Our review suggests that BRCA1/2 might have a role as a risk factor for colorectal, gastric and OeC, albeit with differences among these diseases: In particular BRCA1 seems to be much more frequently mutated in CRC whereas BRCA2 appears to be much more closely associated with gastric and OeC. Early-onset cancer seems to be also associated with BRCA1/2 mutations and a few studies suggest a positive prognostic role of these mutations. The assessment of a potentially predictive role of these mutations is hampered by the fact that most patients with these diseases have been treated with platinum compounds, where it is expected that a higher probability of response should be seen. A few clinical trials focused on poly (ADP-ribose) polymerase inhibitors use in GI cancers are currently ongoing.
| S-EPMC8317649 | biostudies-literature
Project description: Not available
| S-EPMC10493642 | biostudies-literature
Project description:A case report of a 66 year old male patient with COVID 19 who presented late in the clinical course and subsequently developed respiratory failure requiring intubation, after initially experiencing diarrhoea.
| S-EPMC8116635 | biostudies-literature
Project description:ObjectiveOnly 17% of adolescents with type 1 diabetes (T1D) are currently meeting their glycemic targets despite advances in diabetes technologies. Self-management behaviors and challenges specific to use of diabetes technologies are insufficiently studied in adolescents. We aimed to describe the experience of diabetes technology self-management, including facilitators and barriers, among preteens/adolescents with low and high A1C.Research design and methodsYouth (10-18 years of age) with T1D who use insulin pump therapy were recruited from the larger quantitative cohort of a mixed methods study for participation in semi-structured qualitative interviews. Maximum variability sampling was used to recruit youth with A1C <7.5% (n = 5) and A1C >9% (n = 5). Participants' personal insulin pump and continuous glucose monitoring data were downloaded and served as a visual reference. Interviews were analyzed using a qualitative descriptive approach.ResultsParticipants were 50% female with a median age of 14.9 years and 80% used CGM. The sample was predominantly white (90.0%). Analysis produced four major themes, Bad Day, Expect the Unexpected, Nighttime Dependence, and Unpredictability, It's Really a Team and interconnecting subthemes. Youth characterized ''Bad Days'' as those requiring increased diabetes focus and self-management effort. The unpredictability (''Expect the Unexpected'') of glucose outcomes despite attention to self-management behaviors was considerable frustration.ConclusionsDiabetes devices such as insulin pumps are complex machines that rely heavily on individual proficiency, surveillance, and self-management behaviors to achieve clinical benefit. Our findings highlight the dynamic nature of self-management and the multitude of factors that feed youths' self-management behaviors.
| S-EPMC8530879 | biostudies-literature
Project description:Rare, atypical ophthalmological conditions in adults include bulbar conjunctival plexiform schwannomas, which are usually asymptomatic. Few case reports in the literature indicate the presence of orbital/conjunctival schwannomas in adult patients and, rarely, among children under the age of 12. We report a case of a 5-year-old girl who presented in an outpatient clinic with inferior temporal conjunctival nonpigmented cystic lesion of a 10 × 10 mm size. Upon examination, we could not identify a feeding vessel. The mass was mobile and not fixed to the sclera. The history indicated a 1-year duration but the mass in the left eye had progressively increased in size during the last 2 months prior to presentation. There was no traumatic injury or past history of ophthalmic surgery. Surgical excision of the cyst was sucessfully performed, and histopathological examination confirmed bulbar conjunctival plexiform schwannoma diagnosis. Upon regular follow-up evaluation, there was no evidence of recurrence or malignant transformation. Although it is extremely rare to encounter conjunctival schwannomas in children, it should be considered in ovoidal well-circumscribed orbital swellings, particularly those that appear with no history of trauma or surgery to the eye. Surgical excision is effective and safe therapeutic intervention. Plain language summary A 5-year-old girl consulted our ophthalmology clinic for an unusually large swelling in her left eye. It had been increasing in size over the last 2 months before the consultation. She reported no injury or surgery at the swelling site. Apart from the mass, no other abnormality was noted. The family agreed to the surgical removal of the mass, which was performed. Pathological examination revealed a rare tumor called a bulbar conjunctival plexiform schwannoma. This case report is of interest as this type of tumor is rare in children. This case report confirms that surgical removal of these tumors is safe, feasible, and effective as a treatment for this rare condition.
| S-EPMC10285596 | biostudies-literature
Project description:There is considerable evidence that the cerebellum has a vital role in motor learning by constructing an estimate of the sensory consequences of movement. Theory suggests that this estimate is compared with the actual feedback to compute the sensory prediction error. However, direct proof for the existence of this comparison is lacking. We carried out a trial-by-trial analysis of cerebellar neurons during the execution and adaptation of voluntary head movements and found that neuronal sensitivities dynamically tracked the comparison of predictive and feedback signals. When the relationship between the motor command and resultant movement was altered, neurons robustly responded to sensory input as if the movement was externally generated. Neuronal sensitivities then declined with the same time course as the concurrent behavioral learning. These findings demonstrate the output of an elegant computation in which rapid updating of an internal model enables the motor system to learn to expect unexpected sensory inputs.
| S-EPMC6102711 | biostudies-literature
Project description:Over a century after the discovery of the complement system, the first complement therapeutic was approved for the treatment of paroxysmal nocturnal hemoglobinuria (PNH). It was a long-acting monoclonal antibody (aka 5G1-1, 5G1.1, h5G1.1, and now known as eculizumab) that targets C5, specifically preventing the generation of C5a, a potent anaphylatoxin, and C5b, the first step in the eventual formation of membrane attack complex. The enormous clinical and financial success of eculizumab across four diseases (PNH, atypical hemolytic uremic syndrome (aHUS), myasthenia gravis (MG), and anti-aquaporin-4 (AQP4) antibody-positive neuromyelitis optica spectrum disorder (NMOSD)) has fueled a surge in complement therapeutics, especially targeting diseases with an underlying complement pathophysiology for which anti-C5 therapy is ineffective. Intensive research has also uncovered challenges that arise from C5 blockade. For example, PNH patients can still face extravascular hemolysis or pharmacodynamic breakthrough of complement suppression during complement-amplifying conditions. These "side" effects of a stoichiometric inhibitor like eculizumab were unexpected and are incompatible with some of our accepted knowledge of the complement cascade. And they are not unique to C5 inhibition. Indeed, "exceptions" to the rules of complement biology abound and have led to unprecedented and surprising insights. In this review, we will describe initial, present and future aspects of protein inhibitors of the complement cascade, highlighting unexpected findings that are redefining some of the mechanistic foundations upon which the complement cascade is organized.
| S-EPMC9852015 | biostudies-literature
Project description:Mechanisms supporting human ultra-cooperativeness are very much subject to debate. One psychological feature likely to be relevant is the formation of expectations, particularly about receiving cooperative or generous behavior from others. Without such expectations, social life will be seriously impeded and, in turn, expectations leading to satisfactory interactions can become norms and institutionalize cooperation. In this paper, we assess people's expectations of generosity in a series of controlled experiments using the dictator game. Despite differences in respective roles, involvement in the game, degree of social distance or variation of stakes, the results are conclusive: subjects seldom predict that dictators will behave selfishly (by choosing the Nash equilibrium action, namely giving nothing). The majority of subjects expect that dictators will choose the equal split. This implies that generous behavior is not only observed in the lab, but also expected by subjects. In addition, expectations are accurate, matching closely the donations observed and showing that as a society we have a good grasp of how we interact. Finally, correlation between expectations and actual behavior suggests that expectations can be an important ingredient of generous or cooperative behavior.
| S-EPMC5307963 | biostudies-literature