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Two illustrations integrate current knowledge about severe acute respiratory syndrome (SARS) coronaviruses and their life cycle. They have been widely used in education and outreach through free distribution as part of a coronavirus-related resource at Protein Data Bank (PDB)-101, the education portal of the RCSB PDB. Scientific sources for creation of the illustrations and examples of dissemination and response are presented.
The illustration is an important tool to aid in the description and understanding of anatomy, and penguins (Aves: Sphenisciformes: Spheniscidae) are an important clade in environmental monitoring, paleontology, and other research fields. Traditionally, anatomic illustration has been informed by dissection. More recently, micro-computed tomography (micro-CT) has proven to be a powerful tool for three-dimensional anatomic imaging, although larger specimens are more challenging to image due to increased X-ray attenuation. Here, we used traditional dissection and micro-CT to illustrate the skulls of Aptenodytes patagonicus, Eudyptula minor, and Pygoscelis papua, and the extracranial soft tissue of E. minor. Micro-CT prevented the loss of orientation, disarticulation, and distortion of bones that might result from cleaning and drying skulls, while immobilization was achieved by freezing the specimens before imaging. All bony elements in the head were accurately depicted. Fixing, dehydrating, and diffusion staining with iodine (diceCT) enabled the identification of muscles and other large nonmineralized structures, but specimen preparation precluded the ability to show smaller nerves and vessels. The results presented here provide a guide for anatomic studies of penguins and our summary of sample preparation and imaging techniques are applicable for studies of other similarly sized biological specimens.
Decontamination helps limit environmental transmission of infectious agents. It is required for the safe re-use of contaminated medical, laboratory and personal protective equipment, and for the safe handling of biological samples. Heat treatment is a common decontamination method, notably used for viruses. We show that for liquid specimens (here, solution of SARS-CoV-2 in cell culture medium), virus inactivation rate under heat treatment at 70°C can vary by almost two orders of magnitude depending on the treatment procedure, from a half-life of 0.86 min (95% credible interval: [0.09, 1.77]) in closed vials in a heat block to 37.00 min ([12.65, 869.82]) in uncovered plates in a dry oven. These findings suggest a critical role of evaporation in virus inactivation via dry heat. Placing samples in open or uncovered containers may dramatically reduce the speed and efficacy of heat treatment for virus inactivation. Given these findings, we reviewed the literature temperature-dependent coronavirus stability and found that specimen containers, and whether they are closed, covered, or uncovered, are rarely reported in the scientific literature. Heat-treatment procedures must be fully specified when reporting experimental studies to facilitate result interpretation and reproducibility, and must be carefully considered when developing decontamination guidelines.
It is increasingly recognized that the presence of comorbidities substantially contributes to the disease burden in patients with heart failure (HF). Several reports have suggested that clustering of comorbidities can lead to improved characterization of the disease phenotypes, which may influence management of the individual patient. Therefore, we aimed to cluster patients with HF based on medical comorbidities and their treatment and, subsequently, compare the clinical characteristics between these clusters.
Decontamination helps limit environmental transmission of infectious agents. It is required for the safe reuse of contaminated medical, laboratory, and personal protective equipment, and for the safe handling of biological samples. Heat treatment is a common decontamination method, notably used for viruses. We show that for liquid specimens (here, solution of SARS-CoV-2 in cell culture medium), the virus inactivation rate under heat treatment at 70°C can vary by almost two orders of magnitude depending on the treatment procedure, from a half-life of 0.86 min (95% credible interval [CI] 0.09, 1.77) in closed vials in a heat block to 37.04 min (95% CI 12.64, 869.82) in uncovered plates in a dry oven. These findings suggest a critical role of evaporation in virus inactivation via dry heat. Placing samples in open or uncovered containers may dramatically reduce the speed and efficacy of heat treatment for virus inactivation. Given these findings, we reviewed the literature on temperature-dependent coronavirus stability and found that specimen container types, along with whether they are closed, covered, or uncovered, are rarely reported in the scientific literature. Heat-treatment procedures must be fully specified when reporting experimental studies to facilitate result interpretation and reproducibility, and must be carefully considered when developing decontamination guidelines. IMPORTANCE Heat is a powerful weapon against most infectious agents. It is widely used for decontamination of medical, laboratory, and personal protective equipment, and for biological samples. There are many methods of heat treatment, and methodological details can affect speed and efficacy of decontamination. We applied four different heat-treatment procedures to liquid specimens containing SARS-CoV-2. Our results show that the container used to store specimens during decontamination can substantially affect inactivation rate; for a given initial level of contamination, decontamination time can vary from a few minutes in closed vials to several hours in uncovered plates. Reviewing the literature, we found that container choices and heat treatment methods are only rarely reported explicitly in methods sections. Our study shows that careful consideration of heat-treatment procedure-in particular the choice of specimen container and whether it is covered-can make results more consistent across studies, improve decontamination practice, and provide insight into the mechanisms of virus inactivation.
The problem of poor reproducibility of scientific findings has received much attention over recent years, in a variety of fields including psychology and neuroscience. The problem has been partly attributed to publication bias and unwanted practices such as p-hacking. Low statistical power in individual studies is also understood to be an important factor. In a recent multisite collaborative study, we mapped brain anatomical left-right asymmetries for regional measures of surface area and cortical thickness, in 99 MRI datasets from around the world, for a total of over 17,000 participants. In the present study, we revisited these hemispheric effects from the perspective of reproducibility. Within each dataset, we considered that an effect had been reproduced when it matched the meta-analytic effect from the 98 other datasets, in terms of effect direction and significance threshold. In this sense, the results within each dataset were viewed as coming from separate studies in an "ideal publishing environment," that is, free from selective reporting and p hacking. We found an average reproducibility rate of 63.2% (SD = 22.9%, min = 22.2%, max = 97.0%). As expected, reproducibility was higher for larger effects and in larger datasets. Reproducibility was not obviously related to the age of participants, scanner field strength, FreeSurfer software version, cortical regional measurement reliability, or regional size. These findings constitute an empirical illustration of reproducibility in the absence of publication bias or p hacking, when assessing realistic biological effects in heterogeneous neuroscience data, and given typically-used sample sizes.
Gastrointestinal stromal tumors (GISTs) very rarely metastasize to the vertebrae. Tyrosine kinase inhibitors (TKIs) confer favorable long-term survival and durable disease control for metastatic disease. Here, we reviewed a case and the literature to determine the various management options, and neurological outcomes for these patients.
Magnetic resonance spectroscopy (MRS) allows the analysis of biochemical processes non-invasively and in vivo. Still, its application in clinical diagnostics is rare. Routine MRS is limited to spatial, chemical and temporal resolutions of cubic centimetres, mM and minutes. In fact, the signal of many metabolites is strong enough for detection, but the resonances significantly overlap, exacerbating identification and quantification. Besides, the signals of water and lipids are much stronger and dominate the entire spectrum. To suppress the background and isolate selected signals, usually, relaxation times, J-coupling and chemical shifts are used. Here, we propose methods to isolate the signals of selected molecular groups within endogenous metabolites by using long-lived spin states (LLS). We exemplify the method by preparing the LLSs of coupled protons in the endogenous molecules N-acetyl-L-aspartic acid (NAA). First, we store polarization in long-lived, double spin states, followed by saturation pulses before the spin order is converted back to observable magnetization or double quantum filters to suppress background signals. We show that LLS and zero-quantum coherences can be used to selectively prepare and measure the signals of chosen metabolites or drugs in the presence of water, inhomogeneous field and highly concentrated fatty solutions. The strong suppression of unwanted signals achieved allowed us to measure pH as a function of chemical shift difference.
Psychometric theory offers a range of tests that can be used as supportive evidence of both validity and reliability of instruments aimed at measuring patient-reported outcomes (PRO). The aim of this paper is to illustrate psychometric tests within the Classical Test Theory (CTT) framework, comprising indices that are frequently applied to assess item- and scale-level psychometric properties of PRO instruments.
Meta-analysis, which drives evidence-based practice, typically focuses on the average response of subjects to a treatment. For instance in nutritional research the difference in average weight of participants on different diets is typically used to draw conclusions about the relative efficacy of interventions. As a result of their focus on the mean, meta-analyses largely overlook the effects of treatments on inter-subject variability. Recent tools from the study of biological evolution, where inter-individual variability is one of the key ingredients for evolution by natural selection, now allow us to study inter-subject variability using established meta-analytic models. Here we use meta-analysis to study how low carbohydrate (LC) ad libitum diets and calorie restricted diets affect variance in mass. We find that LC ad libitum diets may have a more variable outcome than diets that prescribe a reduced calorie intake. Our results suggest that whilst LC diets are effective in a large proportion of the population, for a subset of individuals, calorie restricted diets may be more effective. There is evidence that LC ad libitum diets rely on appetite suppression to drive weight loss. Extending this hypothesis, we suggest that between-individual variability in protein appetite may drive the trends that we report. A priori identification of an individual's target intake for protein may help define the most effective dietary intervention to prescribe for weight loss.
Rare diseases are often not fully understood and efforts put in investigating it from patient perspective are usually met with challenges. We performed a systematic literature review (SLR) for the last 20 years in Cushing's Syndrome (CS) to illustrate Patient-Reported Outcome (PRO) challenges, and show what solutions were found.PROs and other Clinical Outcome Assessment (COA) used with CS patients were reviewed in 36 studies. Two CS-specific Health Related Quality of Life (HRQL) measures were identified (i.e., CushingQoL, Tuebingen CD-25), as well as depression and neurocognitive measures. For CS-specific HRQL measures, the CushingQoL was the most widely used measure due in part to being the first CS-specific HRQL measure developed. With algorithms mapping the CushingQoL to both the SF-6D and EQ-5D, the CushingQoL could be used to facilitate economic modelling studies in the absence of a generic HRQL measure. While the CushingQoL offers only the global scale and two subscales compared to the six subscales of the Tuebingen CD-25, there is not yet adequate statistical validation data available for the Tuebingen CD-25 to suggest it can withstand the scrutiny of review by multiple stakeholders. Results of this review indicate that the inclusion of a measure of depressive symptoms, such as the BDI-II or similar measure, would be reasonable to include given the high level of comorbidity of depression among CS patients. A brief neurocognitive performance outcome, such as Trail Making tasks A and D or Digit Symbol, could help inform the interpretation of HRQL results. Neurocognitive differences may be an unassessed mediator of HRQL outcomes, partly accounting for the persistence of depressive symptoms and HRQL deficits despite treatment. Results suggest that HRQL improvements are possible within this population. These results are limited by small sample sizes and pre/post study design.CS showcases the difficulties encountered in measuring PROs in rare diseases. A solution for this specific case was developed in the form of dedicated PRO instruments, the CushingQOL and the Tuebingen-25. However, some aspects of CS may not be fully answered or not yet validated (e.g., depressive and cognitive symptoms). Further research needs to be done to address them.
Mustached bats, Pteronotus parnellii, are highly social and vocal. Individuals of this species roost in tight clusters, and emit an acoustically rich repertoire of calls whose behavioral significance is largely unknown. We recorded their social and vocal behaviors within a colony housed under semi-natural conditions. We also quantified the spatial spread of each bat's roosting location and discovered that this was relatively fixed and roughly confined to an individual's body width. The spatial precision in roosting was accompanied by an equally remarkable match between specific vocalizations and well-timed, discrete, identifiable postures/behaviors, as revealed by logistic regression analysis. The bodily behaviors included crouching, marking, yawning, nipping, flicking, fighting, kissing, inspecting, and fly-bys. Two echolocation-like calls were used to maintain spacing in the colony, two noisy broadband calls were emitted during fights, two tonal calls conveyed fear, and another tonal call signaled appeasement. Overall, the results establish that mustached bats exhibit complex social interactions common to other social mammals. The correspondence of relatively low frequency and noisy, broadband calls with aggression, and of tonal, high frequency calls with fear supports Morton's Motivation-Structure hypothesis, and establishes a link between motivation and the acoustic structure of social calls emitted by mustached bats.
Cognitive tests currently used in healthcare and research settings do not account for bias in performance that arises due to cultural context. At present there are no universally accepted steps or minimum criteria for culturally adapting cognitive tests. We propose a methodology for developing specific guidelines to culturally adapt a specific cognitive test and used this to develop guidelines for the ACE-III. We then demonstrated their implementation by using them to produce an ACE-III Urdu for a British South Asian population.
Blood-based epigenome-wide association studies that aim at comparing CpG methylation between colorectal cancer (CRC) patients and controls can lead to the discovery of diagnostic or prognostic biomarkers. Numerous confounders can lead to spurious associations. We aimed to see if 5-fluorouracil (5-FU)/leucovorin chemotherapy administered to cases prior to the collection of their blood has an effect on methylation. 304 patients who received treatment and 273 who did not were profiled on the HumanMethylation450 array. Association tests were adjusted for confounders, including proxies for leukocyte cell counts. There were substantial methylation differences between these two groups that vanished once the leukocyte heterogeneity was accounted for. We observed a significant decrease of T cells in the treatment group (CD4+: p=10(-6); CD8+: p=0.036) and significant increase of NK cells (p=0.05) and monocytes (p=0.0006). 5-FU/leucovorin has no effect on global and local blood-based methylation profiles, other than through differences in the leukocyte compositions that the treatment induced.
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