Miracle-dz/UniFAR-FTUs huggingface dataset:
Influence of feed particle size and feed form on productive performance, egg quality, gastrointestinal tract traits, digestive enzymes, intestinal morphology, and nutrient digestibility of laying hens reared in enriched cages.

A total of 640 Lohmann LSL hens were randomly allotted to 4 dietary treatments arranged in 2 × 2 factorial with 2 feed particle sizes (fine and coarse) and 2 feed forms (mash and crumble). The 2 particle sizes were achieved by grinding whole corn and wheat in the hammer mill to pass through 4- and 8-mm sieves. The laying hen diet was isonutritive, and each diet was fed to 8 enriched cages of 20 hens from 21 to 52 wk of age. Screen size and feed form did not affect feed intake, egg production, egg weight, egg mass, and quality traits of the eggs, except for yolk color score, which decreased with crumbling of the feed. Feed conversion ratio was greater (P < 0.01) in hens fed the coarsely ground diet than in hens fed the finely ground diet. Crumbling the feed increased (P < 0.01) feed intake and feed conversion ratio compared to those after mashing. The relative weight of the liver and length of the small intestines were greater (P < 0.05) in hens fed crumble than in hens fed mash. Finely grinding cereals decreased (P < 0.01) the pancreas and gizzard weight compared to those after coarse grinding. The pH of digestive organs showed significant responses to feed form. Crumbling resulted in increased (P < 0.01) pancreatic activities of amylase, while lipase secretion was not affected by the manipulations in screen size and feed form. Ileal villus measurements (villus height, villus height/crypt depth ratio, villus surface area) were greater (P < 0.01) in hens fed crumble than in hens fed mash, whereas particle size had no effect. Total tract digestibility coefficients of crude ash and ether extracts were improved narrowing screen size from 8 to 4 mm. Data illustrated that grinding cereals to pass through a 4-mm screen could improve the efficiency of feed conversion. However, feeding crumbles provided no benefit to productive performance and egg quality, although the absorptive capacity of laying hens increased.
The chloramphenicol/H+ antiporter CraA of Acinetobacter baumannii AYE reveals a broad substrate specificity

OBJECTIVES To identify major facilitator superfamily (MFS)-type chloramphenicol transporters of Acinetobacter baumannii AYE, to characterize its substrate specificity and identify CraA substrate and H+ binding sites. METHODS Five ORFs predicted to encode chloramphenicol transporters were heterologously expressed in Escherichia coli and their substrate specificity was determined by drug susceptibility assays on solid agar medium. CraA transport properties were determined via whole cell fluorescence experiments using ethidium and dequalinium. ACMA quenching was used to characterize the H+/drug antiport process in everted membrane vesicles. The function of CraA in A. baumannii was determined by drug susceptibility assay using A. baumannii ATCC 19606 ΔcraA. RESULTS CraA, ABAYE0913 and CmlA5 are functionally active when overproduced in E. coli. ABAYE0913 conferred resistance to florfenicol and benzalkonium, CmlA5 conferred resistance to chloramphenicol and thiamphenicol, and craA expression resulted in resistance to chloramphenicol, thiamphenicol, florfenicol, ethidium, dequalinium, chlorhexidine, benzalkonium, mitomycin C and TPP+. Cell expressing craA_E38A showed no resistance to all tested drugs, implying that Glu-38 is involved in the binding of drugs and/or protons. Functional assays indicated that substitution of Asp-46 to Ala resulted in severe susceptibility to cationic drugs, chloramphenicol and thiamphenicol. In contrast, Glu-338 is important for the recognition of chloramphenicol, florfenicol, chlorhexidine and dequalinium. CONCLUSIONS This study suggests that CraA has a broad substrate specificity, similar to that of E. coli MdfA. However, due to the presence of three charged residues in the transmembrane region conferring different susceptibility profiles upon substitution to Ala, we postulate that CraA has a different substrate recognition mode compared with MdfA.
Antithrombotics in stable peripheral artery disease

Patients with peripheral artery disease (PAD) are at high risk for ischemic cardiovascular complications. While single antiplatelet therapy (SAPT), predominantly aspirin, has long been the standard antithrombotic treatment in stable PAD, there have now been greater than 40,000 PAD patients randomized to varying antiplatelet and/or anticoagulant regimens. In this review, we provide a summary of the current evidence for antithrombotics in stable PAD, focusing on the rates of major adverse cardiovascular events (MACE), major adverse limb events (MALE), and major bleeding. SAPT has a limited role in the treatment of asymptomatic PAD, particularly in the absence of concomitant coronary artery disease. In symptomatic PAD, SAPT is effective in preventing MACE, though treatment with a thienopyridine appears marginally superior to aspirin. Dual antiplatelet therapy (DAPT) suggests benefit over SAPT in reducing MACE and MALE, though studies to date are not conclusive and/or are associated with excess major bleeding. Combining moderate to high intensity vitamin K antagonists with antiplatelet therapy does not reduce MACE or MALE and increases life-threatening bleeding. Rivaroxaban 2.5 mg BID in addition to aspirin reduces the incidence of both MACE and MALE as compared to aspirin alone, without increasing life-threatening bleeding. This regimen is associated with a reduced severity of MALE when it does occur. Comparisons across antithrombotic trials in PAD are challenging given the heterogeneity of patient populations and the differing assessment of outcomes. The vascular medicine practitioner can reduce ischemic cardiac and limb events, as well as minimize life-threatening bleeding, by choosing the optimal antithrombotic regimen in their PAD patients.
The regulatory protein GADD34 inhibits TRAIL-induced apoptosis via TRAF6/ERK-dependent stabilization of myeloid cell leukemia 1 in liver cancer cells

GADD34 (growth arrest and DNA damage-inducible gene 34) plays a critical role in responses to DNA damage and endoplasmic reticulum stress. GADD34 has opposing effects on different stimuli-induced cell apoptosis events, but the reason for this is unclear. Here, using immunoblotting analyses and various molecular genetic approaches in HepG2 and SMMC-7721 cells, we demonstrate that GADD34 protects hepatocellular carcinoma (HCC) cells from tumor necrosis factor–related apoptosis-inducing ligand (TRAIL)–induced apoptosis by stabilizing a BCL-2 family member, myeloid cell leukemia 1 (MCL-1). We found that GADD34 knockdown decreased MCL-1 levels and that GADD34 overexpression up-regulated MCL-1 expression in HCC cells. GADD34 did not affect MCL-1 transcription but enhanced MCL-1 protein stability. The proteasome inhibitor MG132 abrogated GADD34 depletion–induced MCL-1 down-regulation, suggesting that GADD34 inhibits the proteasomal degradation of MCL-1. Furthermore, GADD34 overexpression promoted extracellular signal-regulated kinase (ERK) phosphorylation through a signaling axis that consists of the E3 ubiquitin ligase tumor necrosis factor receptor–associated factor 6 (TRAF6) and transforming growth factor-β–activated kinase 1 (MAP3K7)–binding protein 1 (TAB1), which mediated the up-regulation of MCL-1 by GADD34. Of note, TRAIL up-regulated both GADD34 and MCL-1 levels, and knockdown of GADD34 and TRAF6 suppressed the induction of MCL-1 by TRAIL. Correspondingly, GADD34 knockdown potentiated TRAIL-induced apoptosis, and MCL-1 overexpression rescued TRAIL-treated and GADD34-depleted HCC cells from cell death. Taken together, these findings suggest that GADD34 inhibits TRAIL-induced HCC cell apoptosis through TRAF6- and ERK-mediated stabilization of MCL-1.
Dominant Role of Young’s Modulus for Electric Power Generation in PVDF–BaTiO3 Composite-Based Piezoelectric Nanogenerator

The electric power output of a piezoelectric nanogenerator (PENG) depends on the various physical parameters of the constituent materials, including the piezoelectric coefficient, Young’s modulus, and dielectric constant. Herein, we report the mechanical and electrical properties of a poly(vinylidene fluoride)–BaTiO3 (PVDF–BTO) composite-based PENG. Variation of the BTO nanoparticle (NP) content enabled the systematic tuning of the physical parameters that are related to power generation in the composite. The Young’s modulus of the PVDF–BTO composite initially increased, and then eventually decreased, with the increasing BTO content, which was probably due to the clustering effect of the high modulus BTO NPs. The dielectric constant of the composite continuously increased as the BaTiO3 content increased. The piezoelectric outputs were greatly enhanced at 10 wt% of BTO, where the Young’s modulus was the highest. These results indicate that the Young’s modulus plays an important role in the piezoelectric power generation of the composite-based PENGs.
A framework for genomics-informed ecophysiological modeling in plants

Dynamic process-based plant models capture complex physiological response across time, carrying the potential to extend simulations out to novel environments and lend mechanistic insight to observed phenotypes. Despite the translational opportunities for varietal crop improvement that could be unlocked by linking natural genetic variation to first-principles based modeling, these models are challenging to apply to large populations of related individuals. Here we use a combination of model development, experimental evaluation, and genomic prediction in Brassica rapa L. to set the stage for future large-scale process-based modeling of intra-specific variation. We develop a new canopy growth sub-model for B. rapa within the process-based model Terrestrial Regional Ecosystem Exchange Simulator (TREES), test input parameters for feasibility of direct estimation with observed phenotypes across cultivated morphotypes and indirect estimation using genomic prediction on a Recombinant Inbred Line population, and explore model performance on an in silico population under non-stressed and mild water stressed conditions. We find evidence that the updated whole plant model has capacity to distill genotype by environment interaction (G x E) into tractable components. The framework presented offers a means to link genetic variation with environment-modulated plant response and serves as a stepping stone towards large-scale prediction of un-phenotyped, genetically-related individuals under un-tested environmental scenarios.
Association of increased B7 protein expression by infiltrating immune cells with progression of gastric carcinogenesis

Abstract B7 negative costimulatory molecules are a group of molecules associated with the occurrence, development, and therapy of cancers. Here, we aimed to determine the clinical significance of PD-L1, B7-H3, and B7-H4 and their expression in CD8 and CD68 positive cells at different stages of gastric carcinogenesis. We detected PD-L1, B7-H3, B7-H4, CD8, and CD68 expression in samples by immunohistochemical staining of 62 chronic superficial gastritis (CSG) samples, 72 chronic atrophic gastritis (CAG) samples, 68 low-grade intraepithelial neoplasia (LIN) samples, 65 high-grade intraepithelial neoplasia (HIN) samples obtained from gastroscopic biopsies and 50 gastric adenocarcinoma (GA) samples obtained from surgical resections. Then we statistically analyzed the expression differences and correlations. Our results indicated that B7 and CD68 expression on infiltrating immune cells was associated with disease progression. However, infiltration of CD8+ cells decreased with disease progression. B7-H3 expression was markedly enhanced at neoplasia and GA stages. B7-H3 in tumor cells was negatively correlated with CD8-expressing cells. Conversely, B7-H3 expression in tumor-infiltrating immune cells was positively correlated with CD68-expressing cells. B7-H4 expression was found in the cell membrane at the stages of gastritis and low-grade neoplasia and was gradually expressed in the cytoplasm at high-grade neoplasia and GA stages. High B7-H4 expression in infiltrating immune cells was also significantly associated with lower CD8-positive and higher CD68-positive cell densities. Increased B7 protein expression by infiltrating immune cells was associated with disease progression, and specifically, the level of B7-H3 expression and localization of B7-H4 expression differed significantly among different stages of gastric carcinogenesis.
Anatomic Characteristics and Clinical Implications of Angiographic Coronary Thrombus: Insights From a Patient-Level Pooled Analysis of SYNTAX, RESOLUTE, and LEADERS Trials

Background—The distribution of thrombus-containing lesions (TCLs) in an all-comer population admitted with a heterogeneous clinical presentation (stable, ustable angina, or an acute coronary syndrome) and treated with percutaneous coronary intervention is yet unclear, and the long-term prognostic implications are still disputed. This study sought to assess the distribution and prognostic implications of coronary thrombus, detected by coronary angiography, in a population recruited in all-comer percutaneous coronary intervention trials. Methods and Results—Patient-level data from 3 contemporary coronary stent trials were pooled by an independent academic research organization (Cardialysis, Rotterdam, the Netherlands). Clinical outcomes in terms of major adverse cardiac events (major adverse cardiac events, a composite of death, myocardial infarction, and repeat revascularization), death, myocardial infarction, and repeated revascularization were compared between patients with and without angiographic TCL. Preprocedural TCL was present in 257 patients (5.8%) and absent in 4193 (94.2%) patients. At 3-year follow-up, there was no difference for major adverse cardiac events (25.3 versus 25.4%; P=0.683); all-cause death (7.4 versus 6.8%; P=0.683); myocardial infarction (5.8 versus 6.0%; P=0.962), and any revascularizations (17.5 versus 17.7%; P=0.822) between patients with and without TCL. The comparison of outcomes in groups weighing the jeopardized myocardial by TCL also did not show a significant difference. TCL were seen more often in the first 2 segments of the right (43.6%) and left anterior descending (36.8%) coronary arteries. The association of TCL and bifurcation lesions was present in 40.1% of the prespecified segments. Conclusions—TCL involved mainly the proximal coronary segments and did not have any effect on clinical outcomes. A more detailed thrombus burden quantification is required to investigate its prognostic implications. Clinical Trial Registration—URL: http://www.clinicaltrials. gov. Unique identifiers: NCT00114972, NCT01443104, NCT00617084.
Leveraging Horizontal Density Differences between Ontologies to Identify Missing Child Concepts: A Proof of Concept

Previously, we investigated pairs of ontologies with local similarities where corresponding "is-a" paths are of different lengths. This indicated the possibility of importing concepts from one ontology into the other. We referred to such structures as diamonds of concepts. In this paper, we address the question whether pairs of identical concepts in pairs of ontologies have the same children in both. Separate reviews of SNOMED CT and NCIt relative to eight other ontologies uncovered differences in child sets. We provide quantitative data concerning these differences. In cases where there are many identical children in two ontologies, the questions arise why one has more children and whether these children are "missing" in the other ontology. We performed randomized controlled trials in which a human expert evaluated the "fit for import" of such potentially missing child concepts. In two out of four studies, statistical significance was achieved in support of algorithmic import.
Acceleration Pattern and Neuromuscular Response of the Spine and Ankle During the Limits-of-Stability Test.

Kuo, FC. Acceleration pattern and neuromuscular response of the spine and ankle during the limits-of-stability test. J Strength Cond Res XX(X): 000-000, 2019-This study aimed to explore the acceleration amplitude, frequency, and electromyography (EMG) activity at the spine, pelvis, and lower extremities under various platform-stability settings. Thirty two young adults (16 men and 16 women) were recruited from a university in Taiwan. A balance system for limits-of-stability testing was used with 2 platform stability settings (i.e., level 4 and static). An inertial motion system and a telemetry EMG system were used to record kinematic and EMG data. Consequently, compared with the level 4 setting, the static-level setting required greater thoracic lateral flexion, pelvic course, and pelvic pitch; greater acceleration amplitudes of the spine, pelvis, and thigh; and greater acceleration frequencies at the shin and ankle. Participants exhibited a significant increase in knee flexion, ankle abduction, foot acceleration, and activity of the rectus femoris and tibialis anterior muscles when the platform stability was decreased. In addition, higher median frequencies of the spine and pelvis and larger amplitudes of the foot were observed under the level 4 setting. The men exhibited a larger range of motion in lumbar joint and thoracic rotation than did the women. To maintain stability, subjects must readjust their head, spine, and ankle movement amplitudes and frequencies depending on the platform stability. The study findings suggest the use of static platform settings for spine control facilitation and unstable platform settings for proprioception and muscle strengthening of lower extremity.
Does co-transcriptional regulation of alternative splicing mediate plant stress responses?

Abstract Plants display exquisite control over gene expression to elicit appropriate responses under normal and stress conditions. Alternative splicing (AS) of pre-mRNAs, a process that generates two or more transcripts from multi-exon genes, adds another layer of regulation to fine-tune condition-specific gene expression in animals and plants. However, exactly how plants control splice isoform ratios and the timing of this regulation in response to environmental signals remains elusive. In mammals, recent evidence indicate that epigenetic and epitranscriptome changes, such as DNA methylation, chromatin modifications and RNA methylation, regulate RNA polymerase II processivity, co-transcriptional splicing, and stability and translation efficiency of splice isoforms. In plants, the role of epigenetic modifications in regulating transcription rate and mRNA abundance under stress is beginning to emerge. However, the mechanisms by which epigenetic and epitranscriptomic modifications regulate AS and translation efficiency require further research. Dynamic changes in the chromatin landscape in response to stress may provide a scaffold around which gene expression, AS and translation are orchestrated. Finally, we discuss CRISPR/Cas-based strategies for engineering chromatin architecture to manipulate AS patterns (or splice isoforms levels) to obtain insight into the epigenetic regulation of AS.
High risk of heart failure associated with desmoglein‐2 mutations compared to plakophilin‐2 mutations in arrhythmogenic right ventricular cardiomyopathy/dysplasia

Previous studies suggested that genetic status affects the clinical course of arrhythmogenic right ventricular cardiomyopathy/dysplasia (ARVC/D) patients. The aim of this study was to compare the outcome of desmoglein‐2 (DSG2) mutation carriers to those who carry the plakophilin‐2 (PKP2) mutation, the most common ARVC/D‐associated gene.
Novel mechanism of resistance to targeted therapies in lung cancer

ABSTRACT We have identified a non-canonical role of0 Notch3 in response to epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor (TKI) therapy, whereby Notch3 associates with β-catenin, resulting in increased catenin beta-1 (CTNNB1, best known as β-catenin) stability and increased survival of drug persister cells (DPCs). Furthermore, combined treatment of an EGFR TKI with a β-catenin inhibitor demonstrated improved therapeutic outcomes in xenograft models.
Intratympanic steroid therapy for refractory sudden sensory hearing loss: a 12-year experience with the Silverstein catheter

Abstract Background: Sudden sensorineural hearing loss (SSNHL) is commonly encountered in clinical practice. Aim/Objective: Determine if local administration of corticosteroids to the inner ear can improve hearing and speech intelligibility after the failure of conventional treatment for SSNHL loss when administered for 10 days after the onset of the hearing loss in a large cohort of 77 patients. Materials and methods: A Silverstein MicroWick™ was placed under local anesthesia and endoscopic control in the round window niche, allowing self-administration of methylprednisolone twice daily for four weeks. Results: An improvement of the pure tone average was shown in 31% of patients. Speech intelligibility improved significantly in 55% of the total cohort and in 34% of the population with a stable pure tone average. Among the 77 patients, 22% used a hearing aid. Only 14% of the patients were hearing-aid users in the group with an improvement in speech intelligibility as opposed to 31% in the failure group. Conclusion and significance: Local administration of steroids to the inner ear through the round window route improves hearing and speech intelligibility in patients after failure of conventional therapy. The use of a hearing aid was reduced by 50% when speech intelligibility was improved.
Integrated Approaches for the Use of Large Datasets to Identify Rational Therapies for the Treatment of Lung Cancers

The benefit and burden of contemporary techniques for the molecular characterization of samples is the vast amount of data generated. In the era of “big data”, it has become imperative that we develop multi-disciplinary teams combining scientists, clinicians, and data analysts. In this review, we discuss a number of approaches developed by our University of Texas MD Anderson Lung Cancer Multidisciplinary Program to process and utilize such large datasets with the goal of identifying rational therapeutic options for biomarker-driven patient subsets. Large integrated datasets such as the The Cancer Genome Atlas (TCGA) for patient samples and the Cancer Cell Line Encyclopedia (CCLE) for tumor derived cell lines include genomic, transcriptomic, methylation, miRNA, and proteomic profiling alongside clinical data. To best use these datasets to address urgent questions such as whether we can define molecular subtypes of disease with specific therapeutic vulnerabilities, to quantify states such as epithelial-to-mesenchymal transition that are associated with resistance to treatment, or to identify potential therapeutic agents in models of cancer that are resistant to standard treatments required the development of tools for systematic, unbiased high-throughput analysis. Together, such tools, used in a multi-disciplinary environment, can be leveraged to identify novel treatments for molecularly defined subsets of cancer patients, which can be easily and rapidly translated from benchtop to bedside.
Trichuris suis Ova in Inflammatory Bowel Disease

Some but not all epidemiological studies suggest that helminth infection in childhood protects against development of inflammatory bowel disease (IBD) in later years. In animal models of IBD, helminths have shown protective effects and changed bacterial flora in the gut. Based on these concepts, small trials and series have been published showing some positive effects of Trichuris suis ova in ulcerative colitis and Crohn's disease. Currently, large randomized placebo-controlled trials are under way. Results remain to be awaited in order to clarify a possible role of T. suis ova in the treatment of IBD.