Miracle-dz/UniFAR-FTUs huggingface dataset:
C. elegans pharyngeal pumping provides a whole organism bio-assay to investigate anti-cholinesterase intoxication and antidotes

Inhibition of acetylcholinesterase by either organophosphates or carbamates causes anti-cholinesterase poisoning. This arises through a wide range of neurotoxic effects triggered by the overstimulation of the cholinergic receptors at synapses and neuromuscular junctions. Without intervention, this poisoning can lead to profound toxic effects, including death, and the incomplete efficacy of the current treatments, particularly for oxime-insensitive agents, provokes the need to find better antidotes. Here we show how the non-parasitic nematode Caenorhabditis elegans offers an excellent tool for investigating the acetylcholinesterase intoxication. The C. elegans neuromuscular junctions show a high degree of molecular and functional conservation with the cholinergic transmission that operates in the autonomic, central and neuromuscular synapses in mammals. In fact, the anti-cholinesterase intoxication of the worm’s body wall neuromuscular junction has been unprecedented in understanding molecular determinants of cholinergic function in nematodes and other organisms. We extend the use of the model organism’s feeding behaviour as a tool to investigate carbamate and organophosphate mode of action. We show that inhibition of the cholinergic-dependent rhythmic pumping of the pharyngeal muscle correlates with the inhibition of the acetylcholinesterase activity caused by aldicarb, paraoxons and DFP exposure. Further, this bio-assay allows one to address oxime dependent reversal of cholinesterase inhibition in the context of whole organism recovery. Interestingly, the recovery of the pharyngeal function after such anti-cholinesterase poisoning represents a sensitive and easily quantifiable phenotype that is indicative of the spontaneous recovery or irreversible modification of the worm acetylcholinesterase after inhibition. These observations highlight the pharynx of C. elegans as a new tractable approach to explore anti-cholinesterase intoxication and recovery with the potential to resolve critical genetic determinants of these neurotoxins’ mode of action.
Accuracy from the slot: Evaluating draft selections in the National Hockey League

The National Hockey League (NHL) entry draft is a process wherein teams make sequential selections from a pool of eligible players. Given the young age of prospects, drafting requires long‐term forecasting of future performance under a high level of uncertainty. This study assessed the selection accuracy across all seven rounds of the draft, as well as between lottery and non‐lottery picks within the first round. NHL performance data were collected for all forwards (N = 956) and defensemen (N = 558) drafted between 2007 and 2014. In both groups, Kruskal‐Wallis H tests conducted between draft rounds revealed a significant, relatively strong, overall effect of draft order on future performance. However, Mann‐Whitney U post‐hoc tests showed projecting future performance of forwards was only accurate in the first two rounds, while for defensemen, selection was only accurate in the first round. Moreover, forwards selected with lottery picks in the first round outperformed their non‐lottery peers offensively but not defensively. As for defensemen, those selected with lottery picks did not differ from their non‐lottery peers in offensive or defensive performance. Our findings highlight substantial inaccuracies in the NHL draft, particularly past the first two rounds of selection. We offer multiple possible explanations driving such inaccuracies that could form the basis for further work in this area.
Comparison and evolutionary analysis of Brassica nucleotide binding site leucine rich repeat (NLR) genes and importance for disease resistance breeding

The Brassica genus contains many agriculturally significant oilseed and vegetable crops, however the crop yield is threatened by a range of fungal and bacterial pathogens. Nucleotide Binding Site Leucine Rich Repeat (NLR) genes play important roles in plant innate immunity. The evolution of NLR genes is influenced by genomic processes and pathogen selection. At the whole genome level, whole genome duplications (WGDs) generate abundant gene copies, most of which are lost during genome fractionation. At sub‐genomic levels, some retained copies undergo duplication forming clusters which facilitate rapid evolution through recombination. The number, distribution and genetic variations of the NLR genes vary among Brassica species and within populations suggesting differential selection pressure exerted by pathogen populations throughout the evolutionary history. A study of the evolution of disease resistance genes in agriculturally important plants such as Brassicas helps gain insights into their function and inform the identification of resistance genes for breeding of resistant lines.
European Registry on Helicobacter pylori management: Single‐capsule bismuth quadruple therapy is effective in real‐world clinical practice

Abstract Background There has been resurgence in the use of bismuth quadruple therapy (proton pump inhibitor, bismuth, tetracycline and metronidazole) for treating Helicobacter pylori infection thanks to a three‐in‐one single‐capsule formulation. Objective To evaluate the effectiveness and safety of the single‐capsule bismuth quadruple therapy. Methods Data were collected in a multicentre, prospective registry of the clinical practice of gastroenterologists on the management of H. pylori infection, where patients were registered at the Asociación Española de Gastroenterologia REDCap database on an electronic case report form until January 2020. Effectiveness by modified intention‐to‐treat and per‐protocol as well as multivariable analysis were performed. Independent factors evaluated were: age, gender, indication, compliance, proton pump inhibitor dose and treatment line. Results Finally, 2100 patients were prescribed single‐capsule bismuth quadruple therapy following the technical sheet (i.e., three capsules every 6 h for 10 days). The majority of these patients were naive (64%), with an average age of 50 years, 64% women and 16% with peptic ulcer. An overall modified intention‐to‐treat effectiveness of 92% was achieved. Eradication was over 90% in first‐line treatment (95% modified intention‐to‐treat, n = 1166), and this was maintained as a rescue therapy, both in second (89% modified intention‐to‐treat, n = 375) and subsequent lines of therapy (third to sixth line: 92% modified intention‐to‐treat, n = 236). Compliance was the factor most closely associated with treatment effectiveness. Adverse events were generally mild to moderate, and 3% of patients reported a severe adverse event, leading to discontinuation of treatment in 1.7% of cases. Conclusions Single‐capsule bismuth quadruple therapy achieved H. pylori eradication in approximately 90% of patients in real‐world clinical practice, both as a first‐line and rescue treatment, with good compliance and a favourable safety profile.
Establishing diagnostic algorithms for SARS-CoV-2 nucleic acid testing in clinical practice

Background: Coronavirus disease 2019 (COVID-19), which is caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has become a global pandemic. Our laboratory initially used a two-step molecular assay, first reported by Corman et al, for SARS-CoV-2 identification (the Taiwan Center for Disease Control [T-CDC] method). As rapid and accurate diagnosis of COVID-19 is required to control the spread of this infectious disease, the current study evaluated three commercially available assays, including the TaqPath COVID-19 Combo kit, the cobas SARS-CoV-2 test, and the Rendu 2019-nCoV Assay kit, to establish diagnostic algorithms for clinical laboratories. Methods: A total of 790 clinical specimens, including nasopharyngeal swabs, throat swabs, sputum, saliva, stool, endotracheal aspirate, and serum were obtained from patients who were suspected or already confirmed to have COVID-19 at the Taipei Veterans General Hospital from February to May 2020. These specimens were tested for SARS-CoV-2 using the different assays and the performance variance between the assays was analyzed. Results: Of the assays we evaluated, the T-CDC method and the TaqPath COVID-19 Combo kit require lots of hands-on practical laboratory work, while the cobas SARS-CoV-2 test and the Rendu 2019-nCoV Assay kit are fully automated detection systems. The T-CDC method and the TaqPath COVID-19 Combo kit showed similar detection sensitivity; however, the T-CDC method frequently delivered false-positive signals for envelope (E) and/or RNA-dependent RNA polymerase (RdRP) gene detection, thus increasing the risk of reporting false-positive results. A manual test-based testing strategy combining the T-CDC method and the TaqPath COVID-19 Combo kit was developed, which demonstrated excellent concordance rates (>99%) with the cobas and Rendu automatic systems. There were a few cases showing discrepant results, which may be due to the varied detection sensitivities as well as targets among the different platforms. Moreover, the concordance rate between the cobas and Rendu assays was 100%. Conclusion: Based on our evaluation, two SARS-CoV-2 diagnostic algorithms, one focusing on the manual assays and the other on the automatic platforms, were proposed. Our results provide valuable information that allows clinical laboratories to implement optimal diagnostic strategies for SARS-CoV-2 testing based on their clinical needs, such as test volume, turn-around time, and staff/resource limitations.
HEMA and alginate-based chondrogenic semi-interpenetrated hydrogels: synthesis and biological characterization

Abstract Cartilage tissue engineering (CTE) has the general objective of restoring and improving damaged cartilage. A very interesting strategy of CTE is to combine different polymers to obtain a viscoelastic material. In this study, we have evaluated the applicability of poly(2-hydroxyethyl methacrylate) networks semi-interpenetrated with sodium alginate for CTE. Alginate-containing hydrogels show an increase in scaffold porosity and swelling capacity, when compared with nonporous poly(2-hydroxyethyl methacrylate) scaffolds. Primary chondrocytes from young rats were cultured on the hydrogels, and an increase in chondrocyte proliferation and chondrocytic markers was observed in alginate-containing hydrogels. Chondrocytic phenotype was preserved on hydrogels containing the lowest amount of crosslinker and initiator (SEMI 3 and SEMI 4). In addition, nitric oxide production by RAW264.7 macrophages grown on hydrogels was tested, and none of the hydrogels showed high levels of this inflammatory marker after 2 days. These results indicate that our alginate-containing hydrogels could be useful for CTE.
The PAX-FOXO1s trigger fast trans-differentiation of chick embryonic neural cells into alveolar rhabdomyosarcoma with tissue invasive properties limited by S phase entry inhibition

The chromosome translocations generating PAX3-FOXO1 and PAX7-FOXO1 chimeric proteins are the primary hallmarks of the paediatric fusion-positive alveolar subtype of Rhabdomyosarcoma (FP-RMS). Despite the ability of these transcription factors to remodel chromatin landscapes and promote the expression of tumour driver genes, they only inefficiently promote malignant transformation in vivo. The reason for this is unclear. To address this, we developed an in ovo model to follow the response of spinal cord progenitors to PAX-FOXO1s. Our data demonstrate that PAX-FOXO1s, but not wild-type PAX3 or PAX7, trigger the trans-differentiation of neural cells into FP-RMS-like cells with myogenic characteristics. In parallel, PAX-FOXO1s remodel the neural pseudo-stratified epithelium into a cohesive mesenchyme capable of tissue invasion. Surprisingly, expression of PAX-FOXO1s, similar to wild-type PAX3/7, reduce the levels of CDK-CYCLIN activity and increase the fraction of cells in G1. Introduction of CYCLIN D1 or MYCN overcomes this PAX-FOXO1-mediated cell cycle inhibition and promotes tumour growth. Together, our findings reveal a mechanism that can explain the apparent limited oncogenicity of PAX-FOXO1 fusion transcription factors. They are also consistent with certain clinical reports indicative of a neural origin of FP-RMS.
Long-term results after aortic valve replacement for bicuspid or tricuspid valve morphology in a Swedish population

Abstract OBJECTIVES Our goal was to study long-term observed and relative survival after first-time aortic valve replacement surgery with or without concomitant coronary artery bypass surgery with reference to valve morphology (i.e. bicuspid vs tricuspid). METHODS Consecutive patients (n = 5086) from 3 Swedish hospitals, operated on between 1 January 2005 and 31 December 2016, were included. The 30-day mortality (n = 116, 2.3%) was excluded from the analysis of long-term observed and relative survival (n = 4970). Observed survival was analysed using Cox regression. Relative survival was calculated as the ratio between observed and expected survival based on data from the general Swedish population, matched for age, sex and calendar year. Risk factors for death were explored using multivariable analysis. RESULTS During the follow-up (median 4.7 years) period, 1157 (23%) patients died. Observed survival excluding 30-day mortality was 96.6%, 82.7% and 57.6% after 1, 5 and 10 years. Compared with the general Swedish population, the relative 1-, 5- and 10-year survival rates were 99.0%, 97.5% and 89.0%. Bicuspid morphology was independently associated with higher observed and relative long-term survival. Renal dysfunction, diabetes, chronic obstructive pulmonary disease, heart failure, smoking and atrial fibrillation were associated with higher long-term mortality. Combined surgery was not associated with higher observed or relative mortality. CONCLUSIONS Patients with a bicuspid morphology had better prognosis, matching that of the general population. With increased age, long-term relative survival compared favourably with survival in the general Swedish population. Adding coronary artery bypass surgery to an aortic valve replacement procedure did not affect long-term outcome.
Development and validation of a 30-day mortality index based on pre-existing medical administrative data from 13,323 COVID-19 patients: The Veterans Health Administration COVID-19 (VACO) Index

Background Available COVID-19 mortality indices are limited to acute inpatient data. Using nationwide medical administrative data available prior to SARS-CoV-2 infection from the US Veterans Health Administration (VA), we developed the VA COVID-19 (VACO) 30-day mortality index and validated the index in two independent, prospective samples. Methods and findings We reviewed SARS-CoV-2 testing results within the VA between February 8 and August 18, 2020. The sample was split into a development cohort (test positive between March 2 and April 15, 2020), an early validation cohort (test positive between April 16 and May 18, 2020), and a late validation cohort (test positive between May 19 and July 19, 2020). Our logistic regression model in the development cohort considered demographics (age, sex, race/ethnicity), and pre-existing medical conditions and the Charlson Comorbidity Index (CCI) derived from ICD-10 diagnosis codes. Weights were fixed to create the VACO Index that was then validated by comparing area under receiver operating characteristic curves (AUC) in the early and late validation cohorts and among important validation cohort subgroups defined by sex, race/ethnicity, and geographic region. We also evaluated calibration curves and the range of predictions generated within age categories. 13,323 individuals tested positive for SARS-CoV-2 (median age: 63 years; 91% male; 42% non-Hispanic Black). We observed 480/3,681 (13%) deaths in development, 253/2,151 (12%) deaths in the early validation cohort, and 403/7,491 (5%) deaths in the late validation cohort. Age, multimorbidity described with CCI, and a history of myocardial infarction or peripheral vascular disease were independently associated with mortality–no other individual comorbid diagnosis provided additional information. The VACO Index discriminated mortality in development (AUC = 0.79, 95% CI: 0.77–0.81), and in early (AUC = 0.81 95% CI: 0.78–0.83) and late (AUC = 0.84, 95% CI: 0.78–0.86) validation. The VACO Index allows personalized estimates of 30-day mortality after COVID-19 infection. For example, among those aged 60–64 years, overall mortality was estimated at 9% (95% CI: 6–11%). The Index further discriminated risk in this age stratum from 4% (95% CI: 3–7%) to 21% (95% CI: 12–31%), depending on sex and comorbid disease. Conclusion Prior to infection, demographics and comorbid conditions can discriminate COVID-19 mortality risk overall and within age strata. The VACO Index reproducibly identified individuals at substantial risk of COVID-19 mortality who might consider continuing social distancing, despite relaxed state and local guidelines.
Can Small-side Games Provide Adequate High-speed Training in Professional Soccer?

Abstract The aim was to compare the running activity in official matches with that achieved in two small-sided games, designed with the same relative area per player but with different constraints and field dimensions, aiming to stimulate high-speed and very-high-speed running. Seventeen young professional players played one 5 vs. 5+5 with 2 floaters, varying in terms of whether there was a change of playing area (SSGCA) or not change (SSGNC). Running activity was monitored using GPS and the following variables were recorded: total distance covered; high-speed distance (18–21 km·h−1); very high-speed distance (>21 km·h−1); peak speed; accelerations and decelerations between 2–3 m·s−2 and above 3 m·s−2. SSGCA achieved statistically higher total distance, high-speed, peak speed and number of accelerations and decelerations than SSGNC (large to small magnitude). Both drills showed statistically greater high speed, number of accelerations and decelerations than official matches (large to small magnitude). Moreover, SSGCA exhibited statistically more total distance and distance at higher speed than official matches (moderate and small magnitude, respectively). In contrast, official matches showed statistically higher peak speeds than both training tasks and more very high speed than SSGNC (large and moderate magnitude, respectively). Coaches could use SSGCA to promote greater running activity in soccer players.
Habitat associations and distribution model for Fuscopannaria leucosticta in Nova Scotia, Canada

Abstract Fuscopannaria leucosticta is a rare and understudied cyanolichen with an interesting and unusual distribution in tertiary relict hotspots worldwide. There is a relatively large population in eastern North America, where it occurs mostly throughout the Appalachian Mountains and reaches its northernmost extent in New Brunswick and Nova Scotia, Canada. The ability to detect this species, and thus determine its habitat requirements, is critical for understanding how it might be affected by human-induced environmental degradation. Maximum entropy modelling with MaxEnt was used to predict the distribution of suitable habitat for this species in Nova Scotia using 62 presence locations, 1405 pseudo-absence locations and four environmental covariates: depth to water table (a proxy for relative soil moisture), distance to the coast and mean annual temperature and precipitation. Our predictive maps identify important habitat features and areas of high suitability in Nova Scotia with an area under the curve value of 0·85. The predicted distribution of this lichen was most affected by temperature. This study elucidates locations as well as species-habitat relationships for F. leucosticta, providing land managers with baseline data that can aid in the discovery of additional populations and provide a better understanding of its ecological requirements which will support the development of sound conservation strategies for this rare lichen.
Management of root rot diseases of eight wheat varieties using resistance and biological control agents techniques

This study is focused on the screening of eight wheat varieties against Fusarium graminearum and Rhizoctonia solani root rot fungal diseases and their management through biological control agets (BCA) treatments under greenhouse conditions in Department of Plant Pathology, University of Nebraska, Lincoln (USA). These two soil-borne pathogens contributing to significant yield reduction and enhanced growth and yield of Wheat varieties (WVs) after BCA treatments. Experimental trails were set up by applying agar plug inoculation and BCA culture suspension techniques. Highest rating against R. solani was observed in WV Seher-2006 (5.0) while lowest shown by Galaxy-2013 (1.5). On the other hand, maximum rating was observed in Seher-2006 (6.25) while minimum in Punjab-2011 (3.0) against F. graminearum. It was observed that T3 and T4 reduced maximum DS of V1 as indicated 1.5 and 1.75. Treatment T4 also showed maximum fresh weight (FW) (0.11g) and dry weight (DW) (0.28g) of root after BCA treatments against R. solani. Maximum FW and DW (0.49g, 0.35g) of V1 roots were also measured against T3 treatment while minimum mass (0.05g and 0.04g) was calculated against T7 (check). However, maximum fresh and dry weight of V7 and V8 roots were observed against T4 treatment. It was noted that all varieties treated with BCA showed more FW and DW of roots as comparison to control (-ve control). However, BCA treatments against all analyzed WVs did not show significant difference. So, all treatments were reduced DS of WVs and increased biomass and yield of wheat plants. Galaxy-2013 variety (V8) was declared as resistance against R. solani for year 2016-17 and three varieties (Faisalabad2008, Millat-2011 and Punjab-2011) were announced as moderately resistant to R. solani root rot. Comparatively, it was estimated that F. graminearum was more vulnerable as comparison to R. solani. The biological control activity of Trichoderma viride and Bacillus subtilis secreted enzymes and secondary metabolites in wheat plants and induced systemic disease resistance against Fusarium graminearum and Rhizoctonia solani. Therefore, it is concluded that BCA treatments are very effective techniques for the management of fungal pathogens without climatic pollution as in chemical spray form.
Pulmonary toxicity of synthetic amorphous silica – effects of porosity and copper oxide doping

Abstract Materials can be modified for improved functionality. Our aim was to test whether pulmonary toxicity of silica nanomaterials is increased by the introduction of: a) porosity; and b) surface doping with CuO; and whether c) these modifications act synergistically. Mice were exposed by intratracheal instillation and for some doses also oropharyngeal aspiration to: 1) solid silica 100 nm; 2) porous silica 100 nm; 3) porous silica 100 nm with CuO doping; 4) solid silica 300 nm; 5) porous silica 300 nm; 6) solid silica 300 nm with CuO doping; 7) porous silica 300 nm with CuO doping; 8) CuO nanoparticles 9.8 nm; or 9) carbon black Printex 90 as benchmark. Based on a pilot study, dose levels were between 0.5 and 162 µg/mouse (0.2 and 8.1 mg/kg bw). Endpoints included pulmonary inflammation (neutrophil numbers in bronchoalveolar fluid), acute phase response, histopathology, and genotoxicity assessed by the comet assay, micronucleus test, and the gamma-H2AX assay. The porous silica materials induced greater pulmonary inflammation than their solid counterparts. A similar pattern was seen for acute phase response induction and histologic changes. This could be explained by a higher specific surface area per mass unit for the most toxic particles. CuO doping further increased the acute phase response normalized according to the deposited surface area. We identified no consistent evidence of synergism between surface area and CuO doping. In conclusion, porosity and CuO doping each increased the toxicity of silica nanomaterials and there was no indication of synergy when the modifications co-occurred.