Miracle-dz/UniFAR-FTUs huggingface dataset:
Is vaccination a viable method to control Johne’s disease caused by Mycobacterium avium subsp. paratuberculosis? Data from 12 million ovine vaccinations and 7.6 million carcass examinations in New South Wales, Australia from 1999–2009

Background Mycobacterium avium subsp. paratuberculosis (MAP) causes Johne’s disease (or paratuberculosis), a chronic wasting disease of ruminants and other animals resulting from granulomatous enteritis. There are increasing concerns that MAP is zoonotic. The prevalence of Johne’s disease is increasing worldwide. In an attempt to control an epidemic of ovine Johne’s disease (OJD) in New South Wales (NSW), a government/industry sponsored voluntary vaccination/on-farm management program commenced in 2000. We report herein an observational study of changes in disease prevalence as vaccination progressed, based on abattoir surveillance data for OJD from 1999 to 2009. We also discuss the epidemiological, policy, regulatory, research, economic and sociological elements that contributed to the development of a mature control program, whose aim was to halt the epidemic spread of OJD in a naïve sheep population. Methods NSW was divided into areas of “High” (HPA), “Medium” (MPA) and “Low” (LPA) OJD prevalence. A killed whole cell vaccine (Gudair®) was administered to sheep from 2000 to 2009. Trained examiners evaluated the viscera of adult sheep carcasses at slaughter for gross evidence of OJD. MAP infection was confirmed by histopathology. Principal findings From 2000–2009, 12 million vaccine doses were administered in NSW (91%; 10.9 million in the HPA). Many of the vaccinated flocks were suffering > 5% annual mortality in adult sheep, with some individual flocks with 10–15% losses attributable to OJD. A total of 7.6 million carcasses were examined (38%; 2.9 million from the HPA). Overall, 16% of slaughter consignments (sheep consigned to the abattoir from a single vendor) were positive for OJD, of which 94% were from the HPA. In the HPA, the percentage of animals with lesions attributable to OJD at slaughter fell progressively from 2.4% (10,406/432,860) at commencement of vaccination in 2000 to 0.8% (1,573/189,564) by 2009. Herd immunity from vaccination in the HPA was estimated at 70% by 2009, the target commonly espoused for an effective control program based on vaccination. This coincided with a progressive decrease in reports of clinical disease and mortalities in vaccinated flocks. Significance We show a decrease in the prevalence of lesions attributable to OJD in NSW concomitant with initiation of voluntary vaccination, on-farm management plans, abattoir monitoring and feedback of animal prevalence data to sheep producers. We conclude that a target of ≤ 1% regional prevalence of OJD affected sheep at slaughter is achievable using these interventions.
Efficacy and safety of normobaric hyperoxia combined with intravenous thrombolysis on acute ischemic stroke patients

ABSTRACT Intravenous thrombolysis elevates the prognostic level of acute ischemic stroke (AIS) patients. Normobaric hyperoxia (NBO) delays the progression of the infarct core and promotes neurological recovery. However, it is uncertain whether NBO can further raise the prognostic level of AIS patients based on intravenous thrombolysis. To explore the efficacy and safety of NBO combined with intravenous thrombolysis on AIS patients. This observational study included anterior circulation stroke patients who received intravenous thrombolysis within 4.5 h after stroke onset. These patients were divided into two groups based on whether or not they received NBO therapy. The baseline data and the prognosis of the two groups were compared. The primary outcome was the proportion of functional independence (modified Rankin Scale 0–2) at 90 days post discharge. A total of 227 patients were included in this study. 125 patients received NBO therapy combined with intravenous thrombolysis, while 102 patients received intravenous thrombolysis only. Overall, the rate of recanalization was 83.3%. Consequently, 101 patients (80.8%) who received NBO combined with intravenous thrombolysis and 63 patients (61.8%) in the control group achieved functional independence (P = 0.002). Multivariable logistic regression analysis showed that NBO combined with intravenous thrombolysis over intravenous thrombolysis alone was associated with 90-day functional independence (OR: 2.318; 95% CI: 1.226–4.381; P = 0.01). This study verified the efficacy and safety of NBO combined with intravenous thrombolysis in AIS patients. Prospective study is needed to further substantiate these findings.
ENT2 facilitates brain endothelial cell penetration and blood-brain barrier transport by a tumor-targeting anti-DNA autoantibody

The blood-brain barrier (BBB) prevents antibodies from penetrating the CNS and limits conventional antibody-based approaches to brain tumors. We now show that ENT2, a transporter that regulates nucleoside flux at the BBB, may offer an unexpected path to circumventing this barrier to allow targeting of brain tumors with an anti-DNA autoantibody. Deoxymab-1 (DX1) is a DNA-damaging autoantibody that localizes to tumors and is synthetically lethal to cancer cells with defects in the DNA damage response. We found that DX1 penetrated brain endothelial cells and crossed the BBB, and mechanistic studies identify ENT2 as the key transporter. In efficacy studies, DX1 crosses the BBB to suppress orthotopic glioblastoma and breast cancer brain metastases. ENT2-linked transport of autoantibodies across the BBB has potential to be exploited in brain tumor immunotherapy, and its discovery raises hypotheses on actionable mechanisms of CNS penetration by neurotoxic autoantibodies in CNS lupus.
peakPantheR, an R package for large-scale targeted extraction and integration of annotated metabolic features in LC–MS profiling datasets

Abstract Summary Untargeted liquid chromatography–mass spectrometry (LC–MS) profiling assays are capable of measuring thousands of chemical compounds in a single sample, but unreliable feature extraction and metabolite identification remain considerable barriers to their interpretation and usefulness. peakPantheR (Peak Picking and ANnoTation of High-resolution Experiments in R) is an R package for the targeted extraction and integration of annotated features from LC–MS profiling experiments. It takes advantage of chromatographic and spectral databases and prior information of sample matrix composition to generate annotated and interpretable metabolic phenotypic datasets and power workflows for real-time data quality assessment. Availability and implementation peakPantheR is available via Bioconductor (https://bioconductor.org/packages/peakPantheR/). Documentation and worked examples are available at https://phenomecentre.github. io/peakPantheR.github. io/ and https://github.com/phenomecentre/metabotyping-dementia-urine. Supplementary information Supplementary data are available at Bioinformatics online.
Erratum to Eliciting Language Samples for Analysis (ELSA): A New Protocol for Assessing Expressive Language and Communication in Autism

Sommer Hassan, Easy Speech Pathology Clinic, 41555 Cook St. #130, Palm Desert, California, USA Collin Lee, Rosemead School of Psychology, Biola University, 13800 Biola Ave, La Mirada, California, United States Mengyuan Xu, 11500 Commerce Park Dr, Reston, Virginia, United States Riley McKechnie, Laboratories of Cognitive Neuroscience, Division of Developmental Medicine, Boston Children’s Hospital, Harvard Medical School, Boston, Massachusetts, USA
Microfluidics sorting enables the isolation of an intact cellular pair complex of CD8+ T cells and antigen-presenting cells in a cognate antigen recognition-dependent manner

Adaptive immune responses begin with cognate antigen presentation-dependent specific interaction between T cells and antigen-presenting cells. However, there have been limited reports on the isolation and analysis of these cellular complexes of T cell-antigen-presenting cell (T/APC). In this study, we successfully isolated intact antigen-specific cellular complexes of CD8+ T/APC by utilizing a microfluidics cell sorter. Using ovalbumin (OVA) model antigen and OT-I-derived OVA-specific CD8+ T cells, we analyzed the formation of antigen-specific and antigen-non-specific T/APC cellular complexes and revealed that the antigen-specific T/APC cellular complex was highly stable than the non-specific one, and that the intact antigen-specific T/APC complex can be retrieved as well as enriched using a microfluidics sorter, but not a conventional cell sorter. The single T/APC cellular complex obtained can be further analyzed for the sequences of T cell receptor Vα and Vβ genes as well as cognate antigen information simultaneously. These results suggested that this approach can be applied for other antigen and CD8+ T cells of mice and possibly those of humans. We believe that this microfluidics sorting method of the T/APC complex will provide useful information for future T cell immunology research.
The Toddler Autism Symptom Inventory: Use in diagnostic evaluations of toddlers

Although symptoms of autism are present early in life and early diagnosis can lead to better outcomes, there is a dearth of validated caregiver-report interviews designed for children under the age of 3 years. We developed the Toddler Autism Symptom Inventory, a semi-structured interview designed to assess the presence and absence of skills and symptoms in children aged 12–36 months. Reliability and validity of items and a cutoff score for likelihood of autism spectrum disorder were established. Specificity and sensitivity of this cutoff were confirmed with a cross-validation sample. The Toddler Autism Symptom Inventory effectively identified most children with autism without excessive false positives. The Toddler Autism Symptom Inventory is a developmentally appropriate caregiver interview for use in diagnostic evaluations of children under age 3 years that offers clearly operationalized diagnostic criteria and a cutoff for autism likelihood for very young children. Lay abstract Determining whether a young child has an autism spectrum disorder requires direct observation of the child and caregiver report of the child’s everyday behaviors. There are few interviews for parents that are specifically designed for children under 3 years of age. The Toddler Autism Symptom Inventory is a new interview that asks caregivers of children age 12–36 months about symptoms of possible autism spectrum disorder. The Toddler Autism Symptom Inventory uses a cutoff score to indicate likelihood for autism spectrum disorder; this cutoff score appears to accurately identify most children who are diagnosed with autism spectrum disorder without identifying too many who do not have autism spectrum disorder. The Toddler Autism Symptom Inventory interview can help clinicians to determine whether a young child shows symptoms suggestive of an autism spectrum disorder.
Direct Simulation Monte Carlo Analysis of Gas Transport in Microporous Structure Based on X-ray Computed Tomography

Introduction The improvement of gas transport characteristics in porous materials is required to increase the current density of polymer electrolyte fuel cells (PEFCs). While the structure and gas transport phenomena of gas diffusion layers, which have a porous structure with a characteristic length scale of ~10 μm, were extensively investigated, those of microporous layers (MPLs) have not been well understood because of the difficulty of the measurements in sub-μm porous structures. This paper describes the analysis of gas transport in MPLs based on the three-dimensional structure obtained from X-ray nano computed tomography (CT). We employed the direct simulation Monte Carlo (DSMC) method [1] in order to accurately analyze the gas transport phenomena where the characteristic length scale of the structure is comparable to the mean free path of gas molecules. The numerical simulation well reproduces the experimentally observed pressure dependence of diffusion resistance originating from the coexistence of Knudsen and molecular diffusion mechanisms. The effect of porous media morphology on gas transport was examined by an analysis of molecular trajectories.
Does a combination treatment of repetitive transcranial magnetic stimulation and occupational therapy improve upper limb muscle paralysis equally in patients with chronic stroke caused by cerebral hemorrhage and infarction?

Abstract The clinical presentation of stroke is usually more severe in patients with intracerebral hemorrhage (ICH) than in those with cerebral infarction (CI); recovery of stroke-related muscle paralysis is influenced and limited by the type of stroke. To date, many patients have been treated by neurorehabilitation; however, the changes in the recovery of motor paralysis depending on the type of stroke, ICH or CI, have not been established. This study aimed to determine this difference in improvement of upper extremity paralysis using 2-week in-hospital NovEl intervention Using Repetitive transcranial magnetic stimulation combined with Occupational therapy (NEURO). We scrutinized the medical records of all patients with poststroke (ICH or CI) upper extremity muscle paralysis using Fugl-Meyer assessments (FMAs) who had been admitted to 6 hospitals between March 2010 and December 2018 for rehabilitation treatment. This was a multiinstitutional, open-label, retrospective cohort study without control patients. We evaluated the effects of NEURO on patients with CI and ICH by dividing them into 2 groups according to the type of stroke, after adjustment for age, sex, dominant hand, affected hand side, time since stroke, and prediction of recovery capacity in the upper extremity. The study included 1716 (CI [n = 876] and ICH [n = 840]) patients who had undergone at least 2 FMAs and had experienced stroke at least 6 months before. The type of stroke had no effect on the outcomes (changes in the FMA-upper extremity score, F[4,14.0] = 2.05, P = .09, partial η2 = 0.01). Patients from all 5 groups equally benefited from the treatment (improvement in FMA scores) according to the sensitivity analysis-stratified analysis (F = 0.08 to 1.94, P > .16, partial η2 < 0.001). We conclude that NEURO can be recommended for chronic stroke patients irrespective of the type of stroke.
Nanocrystals for Improving Oral Bioavailability of Drugs: Intestinal Transport Mechanisms and Influencing Factors

With the limitation of solubility and dissolution rate of insoluble drugs, following oral administration, they would rifely prove poor and volatile bioavailability, which may fail to realize its therapeutic value. The drug nanocrystals are perceived as effective tactic for oral administration of insoluble drugs attributes to possess many prominent properties such as elevating dissolution rate and saturation solubility, high drug loading capacity, and improving oral bioavailability. Based on these advantages, the application of nanocrystals in oral drug delivery has acquired significant achievement, and so far more than 20 products of drug nanocrystals have been confirmed in the market. However, the oral absorption of drug nanocrystals is still facing huge challenges due to the limitation of many factors. Intrinsic properties of the drugs and complex physiological environment of the intestinal tract are the two most important factors affecting the oral bioavailability of drugs. In addition, the research on the multi-aspect mechanisms of nanocrystals promoting gastrointestinal absorption and bioavailability has been gradually deepened. In this review, we summarized recent advances of the nanocrystals delivered orally, and provided an overview to the research progress for crossing the intestinal tract transport mechanisms of the nanocrystals by some new research techniques. Meanwhile, the factors relevant to the transport of drug nanocrystals were also elaborated in detail. Graphical Abstract Graphical Abstract
Occasional Paper : Language , Ideology and the ‘ Scottish Voice ’

In this Occasional Paper, I would like to emphasise one way in which language ideological issues permeate literary discourse in Scotland. Focusing on issues related to Scots, I will analyse two (in my view complementary) introductions to anthologies of texts in Scots published over the past twenty years, and show how they participate in a wider ideological debate on language and society in Scotland.
Ab-initio study of amorphous Germanium

We employ ab-initio molecular dynamics simulations to study the atomic structure of amorphous germanium. The preparation of an amorphous Ge numerical sample is performed by cooling down from the liquid phase. Calculated structural and thermal properties of the amorphous phase result in good agreement with experimental data. This is a necessary step for starting a complete characterization of the pressure effects on the amorphous germanium.
Palatability and Physical and Chemical Defenses in Five Annelid Polychaetes from Tropical Brazilian Beaches

Although researchers have examined numerous marine organisms’ compensatory characteristics to minimize predation pressure, few have investigated the defensive mechanisms of polychaetes, despite their diversity. Thus, our study’s aim was to evaluate the palatability and defensive strategies, both chemical and structural, in the polychaetes Branchiomma luctuosum, Perinereis anderssoni, Phragmatopoma caudata, Eurythoe complanata, and Timarete sp. Another twofold aim was to determine, by comparing our results with the literature, any latitudinal difference in the defensive strategies of E. complanata and to assess defensive mechanisms and palatability in relation to individuals’ mobility, overtness, body regionalization, and color. Specimens were collected at Boa Viagem and Itaipu Beaches in Niterói, Rio de Janeiro, Brazil. In assays, a generalist consumer, the hermit crab Calcinus tibicen, was used to evaluate palatability and defenses. In palatability assays of live tissue of the polychaetes, consumers were offered a fresh piece of each polychaete to gauge their acceptance or rejection; in artificial food assays to test extracts of the polychaetes, artificial bait containing extracts of the polychaetes was offered to crabs to identify any chemical defense. Although the extracts of B. luctuosum, E. complanata, P. caudata (i.e., opercular crown), and Timarete sp. were not palatable to the consumers, extracts of P. anderssoni and P. caudata (i.e., body) were. Moreover, the opercular crown of P. caudata and the branchial crown of B. luctuosum showed evidence of structural and chemical defenses. The results corroborate past findings, suggesting no latitudinal variation in the defensive strategies of E. complanata. In general, less motile and more exposed species, aposematic or dark in color, exhibited greater investment in defensive strategies and unpalatability.
Correlated and geographically predictable Neanderthal and Denisovan legacies are difficult to reconcile with a simple model based on inter-breeding

Although the presence of archaic hominin legacies in humans is taken for granted, little attention has been given as to how the data fit with how humans colonized the world. Here, I show that Neanderthal and Denisovan legacies are strongly correlated and that inferred legacy size, like heterozygosity, exhibits a strong correlation with distance from Africa. Simulations confirm that, once created, legacy size is extremely stable: it may reduce through admixture with lower legacy populations but cannot increase significantly through neutral drift. Consequently, populations carrying the highest legacies are likely to be those whose ancestors inter-bred most with archaics. However, the populations with the highest legacies are globally scattered and are unified, not by having origins within the known Neanderthal range, but instead by living in locations that lie furthest from Africa. Furthermore, the Simons Genome Diversity Project data reveal two distinct correlations between Neanderthal and Denisovan legacies, one that starts in North Africa and increases west to east across Eurasia and into some parts of Oceania, and a second, much steeper trend that starts in Africa, peaking with the San and Ju/’hoansi and which, if extrapolated, predicts the large inferred legacies of both archaics found in Oceania/Australia. Similar ‘double’ trends are observed for the introgression statistic f4 in a second large dataset published by Qin and Stoneking (Qin & Stoneking 2015 Mol. Biol. Evol. 32, 2665–2674 (doi:10.1093/molbev/msv141)). These trends appear at odds with simple models of how introgression occurred though more complicated patterns of introgression could potentially generate better fits. Moreover, substituting archaic genomes with those of great apes yields similar but biologically impossible signals of introgression, suggesting that the signals these metrics capture arise within humans and are largely independent of the test group. Interestingly, the data do appear to fit a speculative model in which the loss of diversity that occurred when humans moved further from Africa created a gradient in heterozygosity that in turn progressively reduced mutation rate such that populations furthest from Africa have diverged less from our common ancestor and hence from the archaics. In this light, the two distinct trends could be interpreted in terms of two ‘out of Africa’ events, an early one ending in Oceania and Australia and a later one that colonized Eurasia and the Americas.
Host personality predicts cuckoo egg rejection in Daurian redstarts Phoenicurus auroreus

In species that are subject to brood parasitism, individuals often vary in their responses to parasitic eggs, with some rejecting the eggs while others do not. While some factors, such as host age (breeding experience), the degree of egg matching and the level of perceived risk of brood parasitism have been shown to influence host decisions, much of the variation remains unexplained. The host personality hypothesis suggests that personality traits of the host influence its response to parasitic eggs, but few studies have tested this. We investigated the relationship between two personality traits (exploration and neophobia) and a physiological trait (breathing rate) of the host, and egg-rejection behaviour in a population of Daurian redstarts Phoenicurus auroreus in northeast China. We first show that exploratory behaviour and the response to a novel object are repeatable for individual females and strongly covary, indicating distinct personality types. We then show that fast-exploring and less neophobic hosts were more likely to reject parasitic eggs than slow-exploring and more neophobic hosts. Variation in breathing rate—a measure of the stress-response—did not affect rejection behaviour. Our results demonstrate that host personality, along the bold-shy continuum, predicts the responses to parasitic eggs in Daurian redstarts, with bold hosts being more likely to reject parasitic eggs.