Miracle-dz/UniFAR-FTUs huggingface dataset:
Mapping Cell Types and Efferent Pathways in the Ascending Relaxin-3 System of the Nucleus Incertus

Abstract Relaxin-3 (Rln3) is an insulin-family peptide neurotransmitter expressed primarily in neurons of the nucleus incertus (NI) of the pontine tegmentum, with smaller populations located in the deep mesencephalon (DpMe) and periaqueductal gray (PAG). Here, we have used targeted recombination at the Rln3 gene locus to generate an Rln3Cre transgenic mouse line, and characterize the molecular identity and axonal projections of Rln3-expressing neurons. Expression of Cre recombinase in Rln3Cre mice, and the expression of Cre-mediated reporters, accurately reflect the expression of Rln3 mRNA in all brain regions. In the NI, Rln3 mRNA is expressed in a subset of a larger population of tegmental neurons that express the neuropeptide neuromedin-b (NMB). These Rln3-expressing and NMB-expressing neurons also express the GABAergic marker GAD2 but not the glutamatergic marker Slc17a6 (VGluT2). Cre-mediated anterograde tracing with adeno-associated viruses (AAVs) shows that the efferents of the Rln3-expressing neurons in the DpMe and PAG are largely confined to the brain regions in which they originate, while the NI-Rln3 neurons form an extensive ascending system innervating the limbic cortex, septum, hippocampus, and hypothalamus. Viral anterograde tracing also reveals the potential synaptic targets of NI-Rln3 neurons in several brain regions, and the distinct projections of Rln3-expressing and non-expressing neurons in the pontine tegmentum. Rabies virus (RV)-mediated transsynaptic retrograde tracing demonstrates a probable synaptic link between NI-Rln3 neurons and GABAergic neurons in the septum, with implications for the modulation of neural activity in the septo-hippocampal system. Together, these results form the basis for functional studies of the NI-Rln3 system.
Genetic variation in natural populations of the large cranberry, Vaccinium macrocarpon Ait. (Ericaceae)'

1816, the large cranberry has become a regionally important small fruit crop in the United States. In order to assess genetic variation in naturally occurring populations of the large cranberry, sampling was conducted at ten sites distributed from Wisconsin east to Massachusetts, and south to Delaware. Starch gel electrophoresis and substrate-specific staining techniques were used to resolve 23 putative Mendelian loci. Population data collected as individual genotypes were analyzed, generating measures of population structure and genetic diversity. All populations were found to exhibit low levels of genetic variation, e.g., expected heterozygosity (Hexp 0.00 + 0.002-0.057 + 0.030). Relative to other plant species, total genetic diversity was extremely low (H, 0.048) with the majority of all genetic variation due to differences among individuals within populations. This genetic homogeneity was corroborated by Nei's (1978) genetic identity which ranged from 0.977 to one. Recent events in the evolutionary history of this taxon are proposed to have played an important role in determining population genetic structure in this species.
Linking root respiration to chemistry and morphology across species

Root respiration is a critical physiological trait involved in root resource acquisition strategies, yet it is less represented in root trait syndrome. Here we compiled a large dataset of root respiration associated with root chemical and morphological traits from 245 plant species. Our results demonstrated that root respiration correlated positively with root nitrogen concentration (RNC) and negatively with root tissue density (RTD) across and within woody and non‐woody species. However, the relationships between root respiration and specific root length (SRL) and root diameter (RD) were weak or even insignificant. Such root respiration–traits relationships were not completely in line with predictions by the root economics spectrum (RES). Furthermore, the principal component analysis showed that root trait syndrome was multidimensional. Root respiration was associated more strongly with the RNC‐RTD axis (the classical RES) than with the orthogonal SRL‐RD axis for woody species, but not for non‐woody species. Collectively, the linkages of root physiological, chemical, and morphological traits provide a better understanding of root trait covariation and root resource acquisition strategies.
Growth Differentiation Factor 15 Provides Prognostic Information Superior to Established Cardiovascular and Inflammatory Biomarkers in Unselected Patients Hospitalized With COVID-19

Supplemental Digital Content is available in the text. Background: Growth differentiation factor 15 (GDF-15) is a strong prognostic marker in sepsis and cardiovascular disease (CVD). The prognostic value of GDF-15 in coronavirus disease 2019 (COVID-19) is unknown. Methods: Consecutive, hospitalized patients with laboratory-confirmed infection with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and symptoms of COVID-19 were enrolled in the prospective, observational COVID Mechanisms Study. Biobank samples were collected at baseline, day 3 and day 9. The primary end point was admission to the intensive care unit or death during hospitalization, and the prognostic performance of baseline and serial GDF-15 concentrations were compared with that of established infectious disease and cardiovascular biomarkers. Results: Of the 123 patients enrolled, 35 (28%) reached the primary end point; these patients were older, more often had diabetes, and had lower oxygen saturations and higher National Early Warning Scores on baseline. Baseline GDF-15 concentrations were elevated (>95th percentile in age-stratified healthy individuals) in 97 (79%), and higher concentrations were associated with detectable SARS-CoV-2 viremia and hypoxemia (both P<0.001). Patients reaching the primary end point had higher concentrations of GDF-15 (median, 4225 [IQR, 3197–5972] pg/mL versus median, 2187 [IQR, 1344–3620] pg/mL, P<0.001). The area under the receiver operating curve was 0.78 (95% CI, 0.70–0.86). The association between GDF-15 and the primary end point persisted after adjusting for age, sex, race, body mass index, estimated glomerular filtration rate, previous myocardial infarction, heart failure, and atrial fibrillation (P<0.001) and was superior and incremental to interleukin-6, C-reactive protein, procalcitonin, ferritin, D-dimer, cardiac troponin T, and N-terminal pro-B-type natriuretic peptide. Increase in GDF-15 from baseline to day 3 was also greater in patients reaching the primary end point (median, 1208 [IQR, 0–4305] pg/mL versus median, –86 [IQR, –322 to 491] pg/mL, P<0.001). Conclusions: GDF-15 is elevated in the majority of patients hospitalized with COVID-19, and higher concentrations are associated with SARS-CoV-2 viremia, hypoxemia, and worse outcome. The prognostic value of GDF-15 was additional and superior to established cardiovascular and inflammatory biomarkers. Registration: URL: https://www.clinicaltrials. gov; Unique identifier: NCT04314232.
CYP2J19 mediates carotenoid colour introgression across a natural avian hybrid zone

It has long been of interest to identify the phenotypic traits that mediate reproductive isolation between related species, and more recently, the genes that underpin them. Much work has focused on identifying genes associated with animal colour, with the candidate gene CYP2J19 identified in laboratory studies as the ketolase converting yellow dietary carotenoids to red ketocarotenoids in birds with red pigments. However, evidence that CYP2J19 explains variation between red and yellow feather coloration in wild populations of birds is lacking. Hybrid zones provide the opportunity to identify genes associated with specific traits. Here we investigate genomic regions associated with colour in red‐fronted and yellow‐fronted tinkerbirds across a hybrid zone in southern Africa. We sampled 85 individuals, measuring spectral reflectance of forecrown feathers and scoring colours from photographs, while testing for carotenoid presence with Raman spectroscopy. We performed a genome‐wide association study to identify associations with carotenoid‐based coloration, using double‐digest RAD sequencing aligned to a short‐read whole genome of a Pogoniulus tinkerbird. Admixture mapping using 104,933 single nucleotide polymorphisms (SNPs) identified a region of chromosome 8 that includes CYP2J19 as the only locus with more than two SNPs significantly associated with both crown hue and crown score, while Raman spectra provided evidence of ketocarotenoids in red feathers. Asymmetric backcrossing in the hybrid zone suggests that yellow‐fronted females mate more often with red‐fronted males than vice versa. Female red‐fronted tinkerbirds mating assortatively with red‐crowned males is consistent with the hypothesis that converted carotenoids are an honest signal of quality.
Effects of aflatoxin on the development of acquired immunity to swine erysipelas.

: The effect of aflatoxin consumption on the development of acquired immunity to swine erysipelas was studied. Twenty-four pigs were divided into 4 groups (6 pigs/group). Two groups were fed a normal diet and 2 groups were fed the same diet but containing aflatoxin. One group from each diet treatment was given a single injection of an erysipelas bacterin, and 21 days later all pigs were given a challenge inoculum of virulent Erysipelothrix rhusiopathiae organisms. On the basis of the response to the challenge inoculation, pigs were classified as immune, partially immune (PI), or susceptible. Three of the vaccinated pigs fed the normal diet were immune, 2 were PI, and 1 was susceptible, whereas none of the vaccinated pigs given the aflatoxin diet were immune, only 1 was PI, and the remainder were susceptible. Two of the nonvaccinated pigs fed the normal diet were PI and 4 were susceptible; all of the nonvaccinated pigs fed the aflatoxin diet were susceptible. It was concluded that aflatoxin consumption interfered with the development of acquired immunity and apparently increased the severity of the E rhusiopathiae infection in unvaccinated pigs.
Schemes and Performance Evaluation Criteria of Korean Association of External Quality Assessment (KEQAS) for Improving Laboratory Testing

External quality assessment (EQA) is important for evaluating clinical laboratories and enhancing their testing quality. EQA schemes are variable; thus, it is crucial that the EQA organizers share their experiences to continuously improve the EQA scheme. The Korean Association of External Quality Assessment Service (KEQAS) has been the leading, authorized EQA institute for the standardization and quality management of laboratory testing in Korean medical institutions since 1976. The EQA scheme underwent a major change in 2016, and the number of EQA programs increased significantly since then. The key changes implemented in EQA scheme include a fully computerized assessment to accelerate feedback and unification of the testing and reporting methods. We provide an overview of the EQA schemes and performance evaluation criteria of the KEQAS and suggest directions for achieving the global harmonization of EQA.
Intrauterine transmission of ovine progressive pneumonia virus.

: Ovine fetuses, newborn lambs, and ovine colostrum were examined for ovine progressive pneumonia virus. The lambs and colostrum were also examined for specific antibody. Virus was isolated from 1 fetus, from 2 newborn lambs, and from most samples of colostrum. The fetus was about 100 days old and was carried by a seronegative ewe in contact with seropositive sheep. Both newborn lambs were carried by seropositive ewes. One lamb was dead at birth; the other lamb was normal and had not nursed. Antibody specific for the virus was present in the colostrum of 12 of 14 seropositive ewes and in the serum of 8 of 11 lambs that had nursed seropositive ewes, but not in the serum of lambs that had not nursed.
Lifetime radiation risk of stochastic effects – prospective evaluation for space flight or medicine

The concept of lifetime radiation risk of stochastic detrimental health outcomes is important in contemporary radiation protection, being used either to calculate detriment-weighted effective dose or to express risks following radiation accidents or medical uses of radiation. The conventionally applied time-integrated risks of radiation exposure are computed using average values of current population and health statistical data that need to be projected far into the future. By definition, the lifetime attributable risk (AR) is an approximation to more general lifetime risk quantities and is only valid for exposures under 1 Gy. The more general quantities, such as excess lifetime risk (ELR) and risk of exposure-induced cancer, are free of dose range constraints, but rely on assumptions concerning the unknown total radiation effect on demographic and health statistical data, and are more computationally complex than AR. Consideration of highly uncertain competing risks for other radiation-attributed outcomes are required in appropriate assessments of time-integrated risks of specific outcomes following high-dose (>1 Gy) exposures, causing non-linear dose responses in the resulting ELR estimate. Being based on the current population and health statistical data, the conventionally applied time-integrated risks of radiation exposure are: (i) not well suited for projections many years into the future because of the large uncertainties in future secular trends in the population-specific disease rates; and (ii) not optimal for application to atypical groups of exposed persons not well represented by the general population. Specifically, medical patients are atypical in this respect because their prospective risks depend strongly on the original diagnosis, the treatment modality, general cure rates, individual radiation sensitivity, and genetic predisposition. Another situation challenging the application of conventional risk quantities is a projection of occupational radiation risks associated with space flight, both due to higher radiation doses and astronauts’ generally excellent health condition due to pre-selection, training, and intensive medical screening. An alternative quantity, named ‘radiation-attributed decrease of survival’ (RADS), known in past general statistical literature as ‘cumulative risk’, is recommended here for applications in space and medicine to represent the cumulative radiation risk conditional on survival until a certain age. RADS is only based on the radiation-attributed hazard rendering an insensitivity to competing risks or projections of current population statistics far into the future. Therefore, RADS is highly suitable for assessing semi-personalised radiation risks after radiation exposures from space missions or medical applications of radiation.
Comprehensive review of lower third molar management: A guide for improved informed consent

Lower third molar removal is the most commonly performed dental surgical procedure. Nevertheless, it is difficult to ensure that all the informed consent forms given to patients are based on the best evidence as many newer publications could change the conclusions of previous research. Therefore, the goal of this review article is to cover existing meta‐analyses, randomized control trials, and related articles in order to collect data for improved and more current informed consent.
Use of interrupted time series methods in the evaluation of health system quality improvement interventions: a methodological systematic review

Background When randomisation is not possible, interrupted time series (ITS) design has increasingly been advocated as a more robust design to evaluating health system quality improvement (QI) interventions given its ability to control for common biases in healthcare QI. However, there is a potential risk of producing misleading results when this rather robust design is not used appropriately. We performed a methodological systematic review of the literature to investigate the extent to which the use of ITS has followed best practice standards and recommendations in the evaluation of QI interventions. Methods We searched multiple databases from inception to June 2018 to identify QI intervention studies that were evaluated using ITS. There was no restriction on date, language and participants. Data were synthesised narratively using appropriate descriptive statistics. The risk of bias for ITS studies was assessed using the Cochrane Effective Practice and Organisation of Care standard criteria. The systematic review protocol was registered in PROSPERO (registration number: CRD42018094427). Results Of 4061 potential studies and 2028 unique records screened for inclusion, 120 eligible studies assessed eight QI strategies and were from 25 countries. Most studies were published since 2010 (86.7%), reported data using monthly interval (71.4%), used ITS without a control (81%) and modelled data using segmented regression (62.5%). Autocorrelation was considered in 55% of studies, seasonality in 20.8% and non-stationarity in 8.3%. Only 49.2% of studies specified the ITS impact model. The risk of bias was high or very high in 72.5% of included studies and did not change significantly over time. Conclusions The use of ITS in the evaluation of health system QI interventions has increased considerably over the past decade. However, variations in methodological considerations and reporting of ITS in QI remain a concern, warranting a need to develop and reinforce formal reporting guidelines to improve its application in the evaluation of health system QI interventions.
Detection of Usutu virus infection in wild birds in the United Kingdom, 2020

In August 2020, as part of a long-term disease surveillance programme, Usutu virus was detected in five Eurasian blackbirds (Turdus merula) and one house sparrow (Passer domesticus) from Greater London, England. This was initially detected by reverse transcription-PCR and was confirmed by virus isolation and by immunohistochemical detection of flavivirus in tissues. Phylogenetic analysis identified Usutu virus African 3.2 lineage, which is prevalent in the Netherlands and Belgium, suggesting a potential incursion from mainland Europe.
An Integrated Genetic and Biochemical Analysis of the Yeast Telomerase Complex

In the budding yeast S. cerevisiae, the telomerase enzyme is composed of a 1.3 kb TLC1 RNA, which forms a complex with Est2 (the catalytic subunit) and two regulatory proteins, Est1 and Est3. Telomerase acts at a particular period of the cell cycle, late S phase, to sufficiently counteract chromosome erosion and cellular senescence. However, the telomerase complex is very limiting in expression, which argues for a highly regulated process for getting telomerase to where it needs to act. Although yeast telomerase has been the subject of intense investigation by numerous laboratories, a high-resolution view of the precise mechanistic contributions by each subunit to telomere homeostasis has not yet been achieved. To address this, I have employed a biochemical method that provides a detailed view of the stoichiometry of the telomerase holoenzyme combined with a genetic strategy intended to characterize the functional surface of telomerase. First, I developed a genetic strategy that targets functionally important residues on the surface of a protein. This identified dominant negative mutations in EST3 that confer a telomere replication defect when over- expressed in a wild-type yeast strain. This approach was continued by other members of the lab and has resulted in a large collection of separation-of-function alleles in each of the three EST genes. The biochemical method relies on a yeast strain designed to allow quantitative immunoprecipitation of the limiting subunit of the holoenzyme (Est2), followed by equivalent detection of each protein subunit by western blotting. I used this stoichiometry assay to evaluate how Est1 associates with a long helical arm on the TLC1 RNA. I also show that an enzyme complex containing Est1 assembles early in the cell cycle, well before telomere elongation occurs, in accordance with prior genetic observations, whereas the Est3 subunit associates much later in the cell cycle. Integrating the mutations from the genetic strategy with the biochemical method has identified four functionally distinct interfaces on Est1, as well as additional interfaces on Est2 and Est3. Finally, I have uncovered evidence that telomerase exists as two separate complexes with different stoichiometries, arguing for yet an additional level of telomerase regulation
The effect of dietary energy and protein level on feather, skin and nodule growth of the ostrich (Struthio camelus)

Accurate diet formulations are required to fulfil the nutrient requirements of birds in order to achieve optimal production. Knowing how the skin, nodule and feather production characteristics vary with diets of different nutrient densities will help in least-cost modelling. Feather growth and nodule development are factors that were previously neglected in ostrich diet formulation, both of which are essential for the development of a predictive production model. In this trial, 120 birds were placed in 15 pens. Varying energy regimes (high, medium and low) and accompanying protein and amino acid profile levels (level 1–5) were assigned ad libitum to each pen. A randomly selected bird from each pen was slaughtered at 1, 35, 63, 103, 159, 168 and 244 days of age. During the slaughter, each bird was weighed, stunned, exsanguinated, defeathered and eviscerated. Feathers from four regions of the skin were plucked and weighed. The shaft diameter of the wing feathers was measured. The nodule size of the tanned skin was measured for each slaughter age. The data were transformed to natural logarithms and regressed against the total feather weight and the total featherless empty body protein weight to set up allometric growth equations. A prediction equation to determine nodule size of the live bird was proposed. Feed cost optimisation is paramount, and results from this study will aid in setting up least-cost optimisation (simulation) formulation models.