bluuebunny/crossref_metadata_2025_split huggingface dataset:
Risk factors of digital dermatitis in feedlot cattle
Authors: Cortes Julian A , Thomas Anice , Hendrick Steve , Janzen Eugene , Pajor Ed A , Orsel Karin 
Published: May 2021

Abstract
Digital dermatitis (DD) has been reported in North American feedlots, although risk factors are not well characterized. Our objectives were to analyze: (1) foot and leg conformation and (2) pen hygiene, as potential variables that predispose feedlot cattle to DD. Production parameters in DD-affected cattle were compared with healthy cattle and with those diagnosed with more commonly known infectious lesion foot rot (FR). In total, 2,854 feedlot cattle in 11 pens in 2 feedlots were assessed (bi-weekly pen walks) throughout the feeding cycle. Pen condition was categorized as: “dry,” “mud present but has good bedding,” “more mud than bedding,” and “excessive mud.” Gait scoring was competed and cattle with abnormal gait or evident foot lesions (i.e., DD or FR) were restrained in a cattle chute for a close foot inspection (n=280), including scoring of foot angle and claw set and hind and side views of rear feet and legs. Cumulative incidence of DD (present or absent) and FR was 2.5% (71/2,854) and 11.6% (331/2,854), respectively. Foot and leg conformation was not significantly different between left and right sides or between cattle with (n=71) and without DD (n=209). Lameness was diagnosed in only 22% of cattle with DD. Cattle with DD gained 0.27 kg/d less compared with healthy cattle (mean ± SD: 1.29 ± 0.29 vs. 1.56 ± 0.27, P&lt;0.05) and 0.4 kg/d less compared with FR (1.29 ± 0.29 vs. 1.69 ± 0.25). Presence of DD was not significantly different between pens with “dry” and “mud present but has good bedding,” but for pens with “more mud than bedding” or “excessive mud,” the risk of cattle having DD cases increased significantly [odds ratio (OR)=8.55, confidence interval (CI): 4.0–18.4 and OR=14.1, CI: 5.9–33.8, respectively]. In conclusion, it is important to keep good pen conditions to reduce the risk of DD, which can be managed through proper stocking density and strategic bedding, irrespective of foot and leg conformation.
Ammonium transporter PsAMT1.2 from Populus simonii functions in nitrogen uptake and salt resistance
Authors: Li Wenxin , Feng Zimao , Zhang Chunxia 
Published: May 2021

Abstract
Ammonium (NH4+) is a primary nitrogen (N) source for many species, and NH4+ uptake is mediated by various transporters. However, the effects of NH4+ transporters on N uptake and metabolism under salt stress remain unclear. In the present study, we investigated the expression characteristics and transport function of PsAMT1.2 in Populus simonii and its role in ammonium uptake and metabolism under salt stress. PsAMT1.2 was localized in the plasma membrane highly expressed in the roots. Heterologous functionality tests demonstrated that PsAMT1.2 mediates NH4+ permeation across the plasma membrane in yeast mutants, restoring growth. A short-term NH4+ uptake experiment showed that PsAMT1.2 is a high-affinity NH4+ transporter with a Km value of 80.603 μM for NH4+. Compared with the wild type (WT, Populus tremula × Populus alba INRA 717-IB4 genotype), PsAMT1.2-overexpressing transgenic poplar grew better, with higher increases in stem height and relative chlorophyll content under both control and salt-stress conditions. PsAMT1.2 overexpression significantly increased the total NH4+ concentration and total N of whole plants under salt stress. The glutamate synthase (GS), glutamine synthetase (GOGAT) and glutamate dehydrogenase (GDH) activities and the total amino acids largely increased in the roots of PsAMT1.2-overexpressing transgenic plants compared with the WT plants under control conditions, suggesting that PsAMT1.2 overexpression promotes NH4+ assimilation and metabolism in poplar roots. Consistent with the increased total amino acid content, GS1.3, GS2 and Fd-GOGAT expression was upregulated in the roots and leaves of the PsAMT1.2-overexpressing transgenic plants compared with the WT plants under salt stress. Collectively, PsAMT1.2 encodes a high-affinity NH4+ transporter crucial to NH4+ uptake and metabolism under salt stress.
Implementing Value-Added Medical Education: Lessons Learned From the Student-Initiated Stanford Frontline COVID-19 Consult Service
Authors: Zhou Bright , Calkins Christopher , Jayaraman Tanvi , Cassells Sandrene , Rotto Torsten , Vaughan Laura , Srinivasan Malathi , Schillinger Erika 
Published: May 2021

Problem
Value-added medical education (VAME) has been difficult to implement due to student and educator constraints. The COVID-19 pandemic caused mass transitions to online learning, removed students from clinical settings, and underscored students’ desires for meaningful VAME opportunities. The authors introduced the Stanford Frontline COVID-19 Consult Service (SFCS), through which off-service medical and physician assistant (PA) students provided assistance to clinicians in the form of rapid research regarding COVID-19 clinical questions.

Approach
The SFCS, a student-derived VAME initiative, was implemented from March to May 2020 by Stanford University medical students, PA students, and faculty. SFCS aligned with not only the interests of clinicians and students but also national accreditation standards. Students attended weekly editorial meetings, didactic sessions on literature reviews and information management, and they underwent rigorous training on the peer review process. After 2 months, the authors expanded the service to local community clinicians.

Outcomes
The SFCS enrolled 16 students, was supported by 13 faculty members, and produced 87 peer-reviewed evidence syntheses. Of the 16 SFCS students, 13 (81%) completed evaluations; of 128 Stanford Primary Care and Population Health clinicians, 48 (38%) completed evaluations. Overall student satisfaction with the SFCS was 4.9/5 (standard deviation [SD] 0.3). Self-assessed achievement of SFCS learning objectives exceeded 90% for all objectives. Overall faculty satisfaction with the SFCS was 4.4/5 (SD 0.8). Most faculty (40/46 [87%]) planned to use the database to answer future COVID-19 questions.

Next Steps
The SFCS is a novel, student-initiated VAME curriculum focused on increasing students’ meaningful contributions to patient care. The authors will track SFCS students throughout their clerkships to gauge clerkship performance/preparedness, and they will develop training for integrating VAME into preclerkship curricula at other institutions. Given its adaptive, student-driven design, the VAME framework used to develop the SFCS empowers students to create their own personalized, experiential learning.
Timing of Intubation in Coronavirus Disease 2019: A Study of Ventilator Mechanics, Imaging, Findings, and Outcomes
Authors: Bavishi Avni A. , Mylvaganam Ruben J. , Agarwal Rishi , Avery Ryan J. , Cuttica Michael J. 
Published: May 2021

Objectives:
Determine the variation in outcomes and respiratory mechanics between the subjects who are intubated earlier versus later in their coronavirus disease 2019 course.

Design:
Retrospective cohort study.

Setting:
Northwestern Memorial Hospital ICUs.

Patients:
All patients intubated for coronavirus disease 2019 between March 2020 and June 2020.

Interventions:
Patients were stratified by time to intubation: 30 subjects were intubated 4–24 hours after presentation and 24 subjects were intubated 5–10 days after presentation. Baseline characteristics, hospitalization, ventilator mechanics, and outcomes were extracted and analyzed. Ten clinically available CT scans were manually reviewed to identify evidence of pulmonary vascular thrombosis and intussusceptive angiogenesis.

Measurements and Main Results:
Median time from symptom onset to intubation was significantly different between the early and late intubation cohorts, with the latter being intubated later in the course of their illness (7.9 vs 11.8 d; p = 0.04). The early intubation cohort had a lower mortality rate than the late intubation cohort (6% vs 30%, p < 0.001) without significantly different respiratory mechanics at the time of intubation. The late intubation cohort was noted to have higher dead space ratio (0.40 vs 0.52; p = 0.03). On review of CT scans, the late intubation cohort also had more dilated peripheral segments on imaging (two segments vs five segments).

Conclusions:
The question as to whether delaying intubation is beneficial or harmful for patients with coronavirus disease 2019-induced hypoxemic respiratory failure has yet to be answered. As our approaches to coronavirus disease 2019 continue to evolve, the decision of timing of intubation remains paramount. Although noninvasive ventilation may allow for delaying intubation, it is possible that there are downstream effects of delayed intubation that should be considered, including the potential for pulmonary vascular thrombosis and intussusceptive angiogenesis with delayed intubation.
Dysbiosis in pre-cancerous mucosa may drive immune dysfunction – a study of immune system: microbiota interaction in familial adenomatous polyposis
Authors: Noble Alistair , Durant Lydia , Dilke Stella M , Man Ripple , Martin Isabel , Patel Roshani , Hoyles Lesley , Pring Edward T , Latchford Andrew , Clark Susan K , Carding Simon R , Knight Stella C 
Published: May 2021

AbstractObjectivesFamilial adenomatous polyposis (FAP) is a condition caused by a constitutional pathogenic variant of the adenomatous polyposis coli (APC) gene that results in intestinal adenoma formation and colorectal cancer (CRC), necessitating pre-emptive colectomy. We sought to examine interaction between the mucosal immune system and commensal bacteria in FAP to test for immune dysfunction that might accelerate tumorigenesis.MethodsColonic biopsies were obtained from macroscopically normal mucosal tissue from 14 healthy donors and 13 patients with FAP during endoscopy or from surgical specimens. Intraepithelial and lamina propria lymphocytes were phenotyped. Intraepithelial microbes were labelled with anti-IgA/IgG and analyzed by flow cytometry.ResultsProportions of resident memory CD103-expressing CD8+and γδ T cell receptor+intraepithelial lymphocytes were dramatically reduced in both left and right colon of patients with FAP compared to healthy controls. In lamina propria, T-cells expressed less CD103 and CD4+CD103+cells expressed less CD73 ectonucleotidase. IgA coating of epithelia-associated bacteria, IgA+peripheral B cells and CD4 T-cell memory responses to commensal bacteria were increased in FAP.ConclusionsLoss of resident memory T-cells and γδ T-cells in mucosal tissue of patients with FAP accompanies intestinal microbial dysbiosis previously reported in this pre-cancerous state and suggests impaired cellular immunity and tumor surveillance. This may lead to barrier dysfunction, possible loss of regulatory T-cell function and excess IgA antibody secretion. Our data are the first to implicate mucosal immune dysfunction as a contributing factor in this genetically driven disease and identify potentially critical pathways in the etiology of CRC.
COVID-19 wastewater based epidemiology: long-term monitoring of 10 WWTP in France reveals the importance of the sampling context
Authors: Lazuka A. , Arnal C. , Soyeux E. , Sampson M. , Lepeuple A.-S. , Deleuze Y. , Pouradier Duteil S. , Lacroix S. 
Published: May 2021

AbstractSARS-CoV-2 wastewater-based epidemiology (WBE) has been advancedas a relevant indicator of distribution of COVID-19 in communities, supporting classical testing and tracing epidemiological approaches. An extensive sampling campaign, including ten municipal wastewater treatment plants, has been conducted in different cities of France over a 20-weeks period, encompassing the second peak of COVID-19 outbreak in France. A well-recognised ultrafiltration - RNA extraction - RT-qPCR protocol was used and qualified, showing 5.5 +/-0.5% recovery yield on heat-inactivated SARS-CoV-2. Importantly the whole, solid and liquid, fraction of wastewater was used for virus concentration in this study.Campaign results showed medium- to strong-correlation between SARS-CoV-2 WBE data and COVID-19 prevalence. To go further, WWTP inlet flow rate and raining statistical relationships were studied and taken into account for each WWTP in order to calculate contextualized SARS-CoV-2 loads. This metric presented improved correlation strengths with COVID-19 prevalence for WWTP particularly submitted and sensitive to rain. Such findings highlighted that SARS-CoV-2 WBE data ultimately require to be contextualised for relevant interpretation.HighlightsFirst study monitoring inlet of 10 WWTPs located in France for SARS-CoV-2 RNA quantification over a 20-weeks period encompassing the second peak of COVID-19 outbreakViral recovery yield was 5.5 % +/-0.5% using heat-inactivated SARS-CoV-2Medium to high Spearman’s correlation strength was observed between SARS-CoV-2 WBE and COVID-19 prevalence dataConsidering sampling context (ei. rain events) improved data consistency and correlation strengthGraphical Abstract
An evidence synthesis approach for combining different data sources illustrated using entomological efficacy of insecticides for indoor residual spraying
Authors: Green Nathan , Agossa Fiacre , Yovogan Boulais , Oxborough Richard , Kitau Jovin , Müller Pie , Constant Edi , Rowland Mark , Tchacaya Emile FS , Benjamin Koudou G , Churcher Thomas S , Betancourt Michael , Sherrard-Smith Ellie 
Published: May 2021

AbstractBackgroundProspective malaria public health interventions are initially tested for entomological impact using standardised experimental hut trials. In some cases, data are collated as aggregated counts of potential outcomes from mosquito feeding attempts given the presence of an insecticidal intervention. Comprehensive data i.e. full breakdowns of probable outcomes of mosquito feeding attempts, are more rarely available. Bayesian evidence synthesis is a framework that explicitly combines data sources to enable the joint estimation of parameters and their uncertainties. The aggregated and comprehensive data can be combined using an evidence synthesis approach to enhance our inference about the potential impact of vector control products across different settings over time.MethodsAggregated and comprehensive data from a meta-analysis of the impact of Actellic® 300CS (Syngenta), an indoor residual spray (IRS) product, used on wall surfaces to kill mosquitoes and reduce malaria transmission, were analysed using a series of statistical models to understand the benefits and limitations of each.ResultsMany more data are available in aggregated format (N = 23 datasets, 5 studies) relative to comprehensive format (N = 3 datasets, 2 studies). The evidence synthesis model was most robust at predicting the probability of mosquitoes dying or surviving and blood-feeding. Generating odds ratios from the correlated Bernoulli random sample indicates that when mortality and blood-feeding are positively correlated, as exhibited in our data, the number of successfully fed mosquitoes will be under-estimated. Analysis of either dataset alone is problematic because aggregated data require an assumption of independence and there are few and variable data in the comprehensive format.ConclusionsWe developed an approach to combine sources from trials to maximise the inference that can be made from such data. Bayesian evidence synthesis enables inference from multiple datasets simultaneously to give a more informative result and highlight conflicts between sources. Advantages and limitations of these models are discussed.Key messagesStatistical models are developed to best infer key mosquito IRS statistics from disparate data sources.Naïve methods, previously adopted, of combining different data sources can create bias and must be explicitly considered.Mosquitoes are highly likely to feed in experimental hut trials using indoor residual spraying of insecticides so the assumption of independence in the probability of mosquitoes dying is reflective of trial data.We provide code for practitioners to implement this approach themselves in both BUGS and Stan languages running from R.
Parallel processing of olfactory and mechanosensory information in the honeybee antennal lobe
Authors: Tiraboschi Ettore , Leonardelli Luana , Segata Gianluca , Rigosi Elisa , Haase Albrecht 
Published: May 2021

AbstractWe report that airflow produces a complex activation pattern in the antennal lobes of the honeybee Apis mellifera. Glomerular response maps provide a stereotypical code for the intensity and the dynamics of mechanical stimuli that is superimposed on the olfactory code. We show responses to modulated stimuli suggesting that this combinatorial code could provide information about the intensity, direction, and dynamics of the airflow during flight and waggle dance communication.
Dysfunctions of the paraventricular hypothalamic nucleus induce hypersomnia in human and mice
Authors: Chen Chang-Rui , Zhong Yu-Heng , Jiang Shan , Xu Wei , Wang Zan , Xiao Lei , Qu Wei-Min , Huang Zhi-Li 
Published: May 2021

AbstractHypersomnolence disorder (HD) is characterized by excessive sleep, which is a common sequela following stroke, infections or tumorigenesis. HD was traditionally thought to be associated with lesions of wake-promoting nuclei. However, lesion of a single, even two or more wake-promoting nucleuses simultaneously did not exert serious HD. The specific nucleus and neural circuitry for HD remain unknown. Here, we observed that three patients with lesions around the paraventricular nucleus of the hypothalamus (PVH) showed hypersomnolence lasting more than 20 h per day and their excessive sleep decreased with the recovery of the PVH area. Therefore, we hypothesized that the PVH might play an essential role in the occurrence of HD. Using multichannel electrophysiological recording and fiber photometry, we found that PVHvglut2 neurons were preferentially active during wakefulness. Chemogenetic activation of PVHvglut2 neurons potently induced 9-h wakefulness, and PVHCRH, PVHPDYN and PVHOT neuronal activation also exerted wakefulness. Most importantly, ablation of PVHvglut2 neurons drastically induced hypersomnia-like behaviors (30.6% reduction in wakefulness). These results indicate that dysfunctions of the PVH is crucial for physiological arousal and pathogenesis underlying HD.
Hierarchical confounder discovery in the experiment–machine learning cycle
Authors: Rogozhnikov Alex , Ramkumar Pavan , Bedi Rishi , Kato Saul , Escola G. Sean 
Published: May 2021

ABSTRACTThe promise of using machine learning (ML) to extract scientific insights from high dimensional datasets is tempered by the frequent presence of confounding variables, and it behooves scientists to determine whether or not a model has extracted the desired information or instead may have fallen prey to bias. Due both to features of many natural phenomena and to practical constraints of experimental design, complex bioscience datasets tend to be organized in nested hierarchies which can obfuscate the origin of a confounding effect and obviate traditional methods of confounder amelioration. We propose a simple non-parametric statistical method called the Rank-to-Group (RTG) score that can identify hierarchical confounder effects in raw data and ML-derived data embeddings. We show that RTG scores correctly assign the effects of hierarchical confounders in cases where linear methods such as regression fail. In a large public biomedical image dataset, we discover unreported effects of experimental design. We then use RTG scores to discover cross-modal correlated variability in a complex multi-phenotypic biological dataset. This approach should be of general use in experiment–analysis cycles and to ensure confounder robustness in ML models.
Orexin A excites the rat olivary pretectal nucleus via OX2 receptor in a daily manner
Authors: Chrobok Lukasz , Alwani Anna , Pradel Kamil , Klich Jasmin Daniela , Lewandowski Marian Henryk 
Published: May 2021

ABSTRACTPronounced environmental changes between the day and night forced living organisms to evolve specialised mechanisms organising their daily physiology, named circadian clocks. Currently, it has become clear that the master clock in the suprachiasmatic nuclei of the hypothalamus is not an exclusive brain site to generate daily rhythms. Indeed, several brain areas, including the subcortical visual system have been recently shown to change their neuronal activity across the daily cycle. Here we focus our investigation on the olivary pretectal nucleus (OPN) – a retinorecipient structure primarily involved in the pupillary light reflex. Using the multi-electrode array technology ex vivo we provide evidence for OPN neurons to elevate their firing during the behaviourally quiescent light phase. Additionally, we report the robust sensitivity to orexin A via the identified OX2 receptor in this pretectal centre, with higher responsiveness noted during the night. Interestingly, we likewise report a daily variation in the response to PAC1 receptor activation, with implications for the convergence of orexinergic and visual input on the same OPN neurons. Altogether, our report is first to suggest a daily modulation of the OPN activity via intrinsic and extrinsic mechanisms, organising its temporal physiology.GRAPHICAL ABSTRACTHIGHLIGHTSNeurons in the olivary pretectal nucleus (OPN) increase their firing during the dayOrexin A robustly excites the OPN via the OX2 receptorOrexin A and the activation of PAC1 receptor are more effective during the night
Comparative transcriptomic analysis reveals translationally relevant processes in mouse models of malaria
Authors: Georgiadou Athina , Dunican Claire , Soro-Barrio Pablo , Lee Hyun Jae , Kaforou Myrsini , Cunnington Aubrey J. 
Published: May 2021

AbstractRecent initiatives to improve translation of findings from animal models to human disease have focussed on reproducibility but quantifying the relevance of animal models remains a challenge. Here we use comparative transcriptomics of blood to evaluate the systemic host response and its concordance between humans with different clinical manifestations of malaria and five commonly used mouse models. Plasmodium yoelii 17XL infection of mice most closely reproduces the profile of gene expression changes seen in the major human severe malaria syndromes, accompanied by high parasite biomass, severe anemia, hyperlactatemia, and cerebral microvascular pathology. However, there is also considerable discordance of changes in gene expression between species and across all models, indicating that the relevance of biological mechanisms of interest in each model should be assessed before conducting experiments. Our data will aid selection of appropriate models for translational malaria research, and the approach is generalizable to other disease models.