Miracle-dz/UniFAR-FTUs huggingface dataset:
Liver Transcriptome Responses to Heat Stress and Newcastle Disease Virus Infection in Genetically Distinct Chicken Inbred Lines

Heat stress results in reduced productivity, anorexia, and mortality in chickens. The objective of the study was to identify genes and signal pathways associated with heat stress and Newcastle disease virus (NDV) infection in the liver of chickens through RNA-seq analysis, using two highly inbred chicken lines (Leghorn and Fayoumi). All birds were held in the same environment until 14 days of age. On day 14, half the birds were exposed to 38 °C with 50% relative humidity for 4 h, then 35 °C until the end of the experiment. The remaining birds were kept at 25 °C throughout the experiment. The heat-treated birds were inoculated at 21 days of age with 107 EID50 (One EID50 unit is the amount of virus that will infect 50 percent of inoculated embryos) NDV La Sota strain to investigate the effects of both heat stress and NDV infection. Physiological parameters were recorded as blood phenotypes at three stages: acute heat (AH), chronic heat (CH1), and chronic heat combined with NDV infection (CH&NDV), at 4 h, 7 days, and 10 days post-initiation of heat treatment, respectively. Our previous work revealed that the heat-resilient Fayoumi line maintained a more stable acid-base balance in their blood compared to the Leghorn line. Liver samples were harvested on both AH and CH&NDV to characterize the transcriptome profiles of these two inbred lines. Both genetic lines and treatments had large impact on the liver transcriptome. Fayoumi birds had more differentially expressed genes (DEGs) than Leghorn birds for both treatments. Metabolic and immune-related genes were on the DEG list, with Fayoumi having more immune-related DEGs than Leghorns, which was confirmed by gene functional enrichment analysis. Weighted correlation network analysis (WGCNA) indicated that the driver genes such as Solute Carrier Family genes could be very important for stabilizing the acid-base balance in Fayoumi birds during heat stress. Therefore, candidate genes such solute carrier family genes could be potential genetic targets that are regulated by Fayoumis to maintain physical hemostasis under heat stress. Differential gene expression showed that Leghorns mainly performed metabolic regulation in response to heat stress and NDV infection, while Fayoumis regulated both immune and metabolic functions. This study provides novel insights and enhances our understandings of liver response to heat stress of heat resilient and susceptible inbred chicken lines.
Rescue of common exon‐skipping mutations in cystic fibrosis with modified U1 snRNAs

In cystic fibrosis (CF), the correction of splicing defects represents an interesting therapeutic approach to restore normal CFTR function. In this study, we focused on 10 common mutations/variants 711+3A>G/C, 711+5G>A, TG13T3, TG13T5, TG12T5, 1863C>T, 1898+3A>G, 2789+5G>A, and 3120G>A that induce skipping of the corresponding CFTR exons 5, 10, 13, 16, and 18. To rescue the splicing defects we tested, in a minigene assay, a panel of modified U1 small nuclear RNAs (snRNAs), named Exon Specific U1s (ExSpeU1s), that was engineered to bind to intronic sequences downstream of each defective exon. Using this approach, we show that all 10 splicing mutations analyzed are efficiently corrected by specific ExSpeU1s. Using complementary DNA‐splicing competent minigenes, we also show that the ExspeU1‐mediated splicing correction at the RNA level recovered the full‐length CFTR protein for 1863C>T, 1898+3A>G, 2789+5G>A variants. In addition, detailed mutagenesis experiments performed on exon 13 led us to identify a novel intronic regulatory element involved in the ExSpeU1‐mediated splicing rescue. These results provide a common strategy based on modified U1 snRNAs to correct exon skipping in a group of disease‐causing CFTR mutations.
A 5-item frailty index for predicting morbidity and mortality following radical prostatectomy: An Analysis of the American College of Surgeons National Surgical Quality Improvement Program (ACS NSQIP) Database.

INTRODUCTION Current preoperative evaluation methods fail to detect the difference in frailty among patients with the same chronological age. Hence, we sought to assess the ability of a simple 5-item frailty index (5-iFI) score to predict surgical outcomes post radical prostatectomy (RP). METHODS The National Surgical Quality Improvement Program (ACS NSQIP) was queried for patients who underwent RP between 2008 to 2017. The 5-iFI score was calculated by assigning a point for each of the following conditions: (1) chronic obstructive pulmonary disease or pneumonia, (2) congestive heart failure, (3) dependent functional status, (4) hypertension, and (5) diabetes. Multivariable regression was performed to assess the association between the 5-iFI score and perioperative outcomes. RESULTS The cohort included 15,546 (46.2%), 14,541 (46.2%), 3,556 (10.6%) patients with 5-iFI scores of 0, 1, and ≥ 2, respectively. Patients older than 65, non-white, and with an ASA ≥ 3 were more likely to have a 5-iFI score ≥ 2 (p<0.0001). Similarly, a 5-iFI ≥ 2 score was associated with higher Clavien-Dindo grades complications (p-trend <0.0001). Additionally, a 5-iFI score ≥ 2 had 1.66 (1.31 - 2.11) and 1.85 (1.39 - 2.46) times the odds of Clavien-Dindo grade ≥ 3 and grade ≥ 4 adverse events, respectively. Moreover, a 5-iFI score ≥ 2 had 28% increased risk of LOS > 1 day (p < 0.0001), and increased incidence of early mortality (p = 0.01). CONCLUSIONS Frailty, as measured by a simple 5-point frailty index, is an independent predictor of adverse outcomes and early mortality in patients undergoing RP. Preoperative frailty assessment may improve risk stratification and patient counseling prior to surgery.
Species redundancy: a redundant concept?

The concept of 'species redundancy' (or 'ecological redundancy') has recently been applied to community and conservation ecology. The suggestion is that, in some communities, some species are 'redundant', i.e. they could be lost without much effect on the structure and functioning of the whole community. In this paper, we have three aims. Firstly we explore the history: the origin and use of the concept. Then we ask what redundancy means in practice: what has to remain constant before we can declare 'redundancy', and how should redundancy be determined? Finally we discuss the value of the concept of 'redundancy' in conservation.
The Geographic Variation of Ambystoma macrodactylum Baird, with the Description of Two New Subspecies

The taxonomic history of the salamander Ambystoma macrodactylum is briefly reviewed. The recently described race A. m. croceum is accepted. Certain differences in color and color pattern of adult animals, especially as concern the dorsal band, indicate the existence of four additional races: A. m. columbianum and A. m. sigillatum, heretofore unrecognized subspecies; A. m. krausei and A. m. macrodactylum, restricted and redefined. For each subspecies, description, distinguishing characteristics, distribution, variations or known local deviants and a list of specimens examined are presented. Sexual dimorphism of the vent is described. Specimens of the four races are pooled into four samples and the means of 14 ratios formed from measurements and counts are compared using a completely randomized Factorial Design, the Analysis of Variance and the Individual Degree of Freedom based on the F distribution. A number of significant differences are demonstrated, lending additional support to the taxonomic separation of the species into the proposed races. A key to adults of the subspecies is given. Life history data pertaining to breeding, larval development and habitat preferences are presented and compared for the various races.
The diagnostic value of 18F-FDG PET/CT in identifying the causes of fever of unknown origin.

BACKGROUND This study investigated the clinical significance of 18F-fluorodeoxyglucose positron emission tomography / computed tomography (18F-FDG PET/CT) in identifying the causes of fever of unknown origin (FUO). METHODS Patients with a fever who received an 18F-FDG PET/CT examination were retrospectively selected. The means of the two groups were compared using an independent-samples t-test. RESULTS Among the 89 included patients, 66 were diagnosed using 18F-FDG PET/CT. The sensitivity, specificity and diagnostic accuracy of 18F-FDG PET/CT for the diagnosis of patients with FUO were 84.5%, 25.8%, and 64.0%, respectively. The detection rates of 18F-FDG PET/CT for neoplastic diseases, infectious diseases and non-infectious inflammatory diseases were 100%, 61.3%, and 75%, respectively. The difference in C-reactive protein (CRP) levels between the two groups was statistically significant. CONCLUSIONS 18F-FDG PET/CT has great clinical importance in diagnosing and identifying causes of FUO and improves the accuracy of FUO diagnosis when combined with serum CRP levels.
Foam Rolling Prescription: A Clinical Commentary.

Behm, DG, Alizadeh, S, Hadjizadeh Anvar, S, Mahmoud, MMI, Ramsay, E, Hanlon, C, and Cheatham, S. Foam rolling prescription: a clinical commentary. J Strength Cond Res XX(X): 000-000, 2020-Although the foam rolling and roller massage literature generally reports acute increases in range of motion (ROM) with either trivial or small performance improvements, there is little information regarding appropriate rolling prescription. The objective of this literature review was to appraise the evidence and provide the best prescriptive recommendations for rolling to improve ROM and performance. The recommendations represent studies with the greatest magnitude effect size increases in ROM and performance. A systematic search of the rolling-related literature found in PubMed, ScienceDirect, Web of Science, and Google Scholar was conducted using related terms such as foam rolling, roller massage, ROM, flexibility, performance, and others. From the measures within articles that monitored ROM (25), strength (41), jump (41), fatigue (67), and sprint (62) variables; regression correlations and predictive quadratic equations were formulated for number of rolling sets, repetition frequency, set duration, and rolling intensity. The analysis revealed the following conclusions. To achieve the greatest ROM, the regression equations predicted rolling prescriptions involving 1-3 sets of 2-4-second repetition duration (time for a single roll in one direction over the length of a body part) with a total rolling duration of 30-120-second per set. Based on the fewer performance measures, there were generally trivial to small magnitude decreases in strength and jump measures. In addition, there was insufficient evidence to generalize on the effects of rolling on fatigue and sprint measures. In summary, relatively small volumes of rolling can improve ROM with generally trivial to small effects on strength and jump performance.
In Vitro Metabolism of DWP16001, a Novel Sodium-Glucose Cotransporter 2 Inhibitor, in Human and Animal Hepatocytes

DWP16001 is currently in a phase 2 clinical trial as a novel anti-diabetes drug for the treatment of type 2 diabetes by selective inhibition of sodium-glucose cotransporter 2. This in vitro study was performed to compare the metabolism of DWP16001 in human, dog, monkey, mouse, and rat hepatocytes, and the drug-metabolizing enzymes responsible for the metabolism of DWP16001 were characterized using recombinant human cytochrome 450 (CYP) and UDP-glucuronosyltransferase (UGT) enzymes expressed from cDNAs. The hepatic extraction ratio of DWP16001 in five species ranged from 0.15 to 0.56, suggesting that DWP16001 may be subject to species-dependent and weak-to-moderate hepatic metabolism. Five phase I metabolites (M1–M5) produced by oxidation as well as three DWP16001 glucuronides (U1–U3) and two hydroxy-DWP16001 (M1) glucuronides (U4, U5), were identified from hepatocytes incubated with DWP16001 by liquid chromatography-high resolution mass spectrometry. In human hepatocytes, M1, M2, M3, U1, and U2 were identified. Formation of M1 and M2 from DWP16001 was catalyzed by CYP3A4 and CYP2C19. M3 was produced by hydroxylation of M1, while M4 was produced by hydroxylation of M2; both hydroxylation reactions were catalyzed by CYP3A4. The formation of U1 was catalyzed by UGT2B7, but UGT1A4, UGT1A9, and UGT2B7 contributed to the formation of U2. In conclusion, DWP16001 is a substrate for CYP3A4, CYP2C19, UGT1A4, UGT1A9, and UGT2B7 enzymes. Overall, DWP16001 is weakly metabolized in human hepatocytes, but there is a potential for the pharmacokinetic modulation and drug–drug interactions, involved in the responsible metabolizing enzymes of DWP16001 in humans.
Efficacy of factory-treated and dip-it-yourself long lasting insecticide-treated bednets against cutaneous leishmaniasis vectors in the sub-Andean region of Colombia: results after two years of use

BACKGROUND Long lasting insecticide-treated nets (LLINs) may be effective for vector control of cutaneous leishmaniasis (CL). Their efficacy, however, has not been sufficiently evaluated. OBJECTIVE To evaluate the large-scale efficacy of LLINs on Lutzomyia longiflocosa entomological parameters up to two years post-intervention in the sub-Andean region of Colombia. METHODS A matched-triplet cluster-randomised study of 21 rural settlements, matched by pre-intervention L. longiflocosa indoor density was used to compare three interventions: dip it yourself (DIY) lambda-cyhalothrin LLIN, deltamethrin LLIN, and untreated nets (control). Sand fly indoor density, feeding success, and parity were recorded using CDC light trap collections at 1, 6, 12, and 24 months post-intervention. FINDINGS Both LLINs reduced significantly (74-76%) the indoor density and the proportion of fully engorged sand flies up to two years post-intervention without differences between them. Residual lethal effects of both LLINs and the use of all nets remained high throughout the two-year evaluation period. CONCLUSIONS Both LLINs demonstrated high efficacy against L. longiflocosa indoors. Therefore, the deployment of these LLINs could have a significant impact on the reduction of CL transmission in the sub-Andean region. The DIY lambda-cyhalothrin kit may be used to convert untreated nets to LLINs increasing coverage.
Predictors of Early Discharge From Early Intervention Services for Psychosis in New York State.

OBJECTIVE Although specialized early intervention services (EISs) for psychosis promote engagement in care, a substantial number of individuals who receive these services are discharged from care earlier than expected. The main goal of this study was to examine predictors of early discharge in a large sample of individuals enrolled in an EIS program in the United States. METHODS This cohort study (N=1,349) used programmatic data from OnTrackNY, an EIS program that delivers evidence-based interventions to youths across New York State experiencing a first episode of nonaffective psychosis. The main outcome was "early discharge," which was operationalized as discharge prior to completing 12 months of treatment. Cox proportional hazard regression models were used to assess the association between sociodemographic, clinical, and support system predictors and early discharge. RESULTS The estimated probability of discharge before 1 year was 32%. Participants who at baseline had poor medication adherence, had no health insurance, were living alone or with nonparental family, or were using cannabis were at higher risk of leaving services within the first 12 months after enrollment. Individuals with higher social functioning were at lower risk of being discharged early from OnTrackNY, but those with higher occupational functioning were at a higher risk. CONCLUSIONS Predictors of early discharge from EISs largely overlapped with previously identified predictors of poor prognosis in early psychosis. However, the association between early discharge and high occupational functioning indicates that trajectories leading up to discharge are heterogeneous.
Coccolith volume of the Southern Ocean coccolithophore Emiliania huxleyi as a possible indicator for palaeo‐cell volume

Coccolithophores are a key functional phytoplankton group and produce minute calcite plates (coccoliths) in the sunlit layer of the pelagic ocean. Coccoliths significantly contribute to the sediment record since the Triassic and their geometry have been subject to palaeoceanographic and biological studies to retrieve information on past environmental conditions. Here, we present a comprehensive analysis of coccolith, coccosphere and cell volume data of the Southern Ocean Emiliania huxleyi ecotype A, subject to gradients of temperature, irradiance, carbonate chemistry and macronutrient limitation. All tested environmental drivers significantly affect coccosphere, coccolith and cell volume with driver‐specific sensitivities. However, a highly significant correlation emerged between cell and coccolith volume with Vcoccolith = 0.012 ± 0.001 * Vcell + 0.234 ± 0.066 (n = 23, r2 = .85, p < .0001, σest = 0.127), indicating a primary control of coccolith volume by physiological modulated changes in cell volume. We discuss the possible application of fossil coccolith volume as an indicator for cell volume/size and growth rate and, additionally, illustrate that macronutrient limitation of phosphorus and nitrogen has the predominant influence on coccolith volume in respect to other environmental drivers. Our results provide a solid basis for the application of coccolith volume and geometry as a palaeo‐proxy and shed light on the underlying physiological reasons, offering a valuable tool to investigate the fossil record of the coccolithophore E. huxleyi.
Molecular Alterations in Spermatozoa of a Family Case Living in the Land of Fires—A First Look at Possible Transgenerational Effects of Pollutants

In our previous work, we reported alterations in protamines/histones ratio, in DNA binding of these proteins and their involvement in DNA oxidative damage in 84% of the young men living in the Land of Fires. In the present work, we extended our findings, evaluating any alterations in spermatozoa of a family case, a father and son, living in this area, to also give a first look at the possibility of transgenerational inherited effects of environmental contaminants on the molecular alterations of sperm nuclear basic proteins (SNBP), DNA and semen parameters. In the father and son, we found a diverse excess of copper and chromium in the semen, different alterations in SNBP content and low DNA binding affinity of these proteins. In addition, DNA damage, in the presence of CuCl2 and H2O2, increased by adding both the father and son SNBP. Interestingly, son SNBP, unlike his father, showed an unstable DNA binding and were able to produce DNA damage even without external addition of CuCl2, in line with a lower seminal antioxidant activity than the father. The peculiarity of some characteristics of son semen could be a basis for possible future studies on transgenerational effects of pollutants on fertility.
Response to Placebo in Fragile X Syndrome Clinical Trials: An Initial Analysis

Fragile X syndrome (FXS) is the leading cause of inherited intellectual disability and autism spectrum disorder. Individuals with FXS often present with a wide range of cognitive deficits and problem behaviors. Educational, behavioral and pharmacological interventions are used to manage these and other complex issues affecting individuals with FXS. Despite the success of preclinical models and early-phase drug clinical studies in FXS, large-scale randomized-controlled trials have failed to meet primary endpoints. Currently, no targeted or disease-modifying treatments for FXS have received regulatory approval. Here, we examined the placebo response in FXS clinical trials conducted between 2006 and 2018. Specifically, we performed a meta-analysis of placebo-treated groups in eight double-blind, randomized controlled trials. Placebo groups demonstrated significant improvements on caregiver-rated efficacy endpoints, which were greater in adolescents and adults than in children. Among the latter measures, the Visual Analog Scale scores displayed the greatest improvements, whereas the positive effects on the Vineland-II Adaptive Behavior Composite and the Aberrant Behavior Checklist-Community/fragile X version were statistically significant in both children and adolescents/adults. Although the Clinical Global Impression scale Improvement appears to have exhibited a substantial placebo effect in multiple clinical trials in FXS, limited data availability for meta-analysis, prevented us from drawing conclusions. No placebo-related improvements were observed in performance-rated measures. These findings raise substantial concerns about placebo effects in outcome measures commonly used in the randomized-controlled trials in FXS and suggest several potential improvements in the study design and implementation of such trials. Considering the small number of trials available for this study, larger and more detailed follow up meta-analyses are needed. Meanwhile, efforts to improve the measurement properties of endpoints and rater training in drug trials in FXS should be prioritized.
Occurrence of Listeria monocytogenes and Escherichia coli in raw sheep milk from farm bulk tanks in Central Italy.

In relation to milk hygiene and safety, the milking phase is considered a critical moment since it represents a probable pathway for the introduction of unwanted microorganisms in the dairy chain. In particular, Listeria monocytogenes (L. monocytogenes) and Escherichia coli ( E. coli ) are known as possible microbial contaminants of raw sheep milk although extensive knowledge regarding their contamination dynamics in sheep farms is still lacking. This study aimed to examine the occurrence and concentration of these microorganisms in milk samples collected from farm bulk tanks in the region of Lazio (Central Italy) and investigate the related risk factors. Over a period of one year, we collected 372 milk samples from 87 sheep farms and administered a questionnaire in order to acquire information regarding relevant farm management variables. The results showed that L. monocytogenes was not present in any of the samples, suggesting that the contamination of sheep bulk tank milk with this pathogen has a low probability. Meanwhile, E. coli was found in almost two thirds of milk samples (61%) but was quantified below 10 2 CFU/ml in most of them (around 75%). Statistical analysis indicated that the presence of E. coli tends to be more probable and counts are significantly higher during the warmest seasons. Unexpectedly, milk collected by hand milking resulted in lower level of contamination. We believe that, although further studies are necessary to clarify some aspects, the reported data contributed to deepen the knowledge about the occurrence of L. monocytogenes and E. coli in raw sheep milk and provided useful data for future risk assessments.