Miracle-dz/UniFAR-FTUs huggingface dataset:
Dietary Supplementation of Lysophospholipids Affects Feed Digestion in Lambs

Simple Summary Previous works showed that supplementation of lysophospholipid as a feed additive improves animal growth and milk yield in beef and dairy cattle production. However, its effects on fattening lambs have not been reported before. In this study, we fed fattening lambs a diet with no or 0.5 g lysophospholipid in a kilogram of diet. We found that lysophospholipid did not or slightly improved the growth of fattening lambs. Feed digestibility, ruminal fermentation parameters and rumen bacterial community were altered, which may be associated with decreased fiber digestion. However, lipase concentration in serum was decreased, which might enhance fat deposition in muscle and thus may increase meat quality. Effects of lysophospholipid on sheep observed in this study are different from those on cattle, which warrants further study. Abstract Five experiments were conducted to examine effects of lysophospholipids (LPL) on live weight gain, nutrient digestibility, ruminal fermentation parameters, serum biochemical parameters and rumen bacterial community profile in fattening lambs. Two dietary treatments (pelleted complete feed supplemented without (control diet; CON) or with 0.05% LPL on dry matter basis) were tested in these experiments. Feed and water were provided ad libitum to lambs. The results showed that average daily gain (ADG) tended to increase or was not affected by LPL supplementation. Compared with CON, the supplementation of LPL resulted in an increase in dry matter, crude protein and organic matter digestibilities, and a decrease in neutral detergent fiber and acid detergent fiber digestibilities. Ruminal pH values did not change with LPL supplementation, but the concentrations of ammonia and total short chain fatty acids (SCFAs) were increased. The molar proportion of major individual SCFAs and the ratio of acetate to propionate were not affected by LPL supplementation. While the activity of lipase was decreased with LPL supplementation, all other serum biochemical parameters did not change. Rumen bacterial community was altered by LPL supplementation with the relative abundance of fibrolytic bacteria in the total bacterial population, such as Prevotella, decreased. In conclusion, LPL supplementation can alter feed digestion, but may not result in consistent positive responses in animal growth performance.
The Staphylococcus aureus ArlRS two‐component system regulates virulence factor expression through MgrA

The Gram‐positive bacterium, Staphylococcus aureus, is a versatile pathogen that can sense and adapt to a wide variety of environments within the human host, in part through its 16 two‐component regulatory systems. The ArlRS two‐component system has been shown to affect many cellular processes in S. aureus, including autolysis, biofilm formation, capsule synthesis and virulence. Yet the molecular details of this regulation remained largely unknown. We used RNA sequencing to identify the ArlRS regulon, and found 70% overlap with that of the global regulator MgrA. These genes included cell wall‐anchored adhesins (ebh, sdrD), polysaccharide and capsule synthesis genes, cell wall remodeling genes (lytN, ddh), the urease operon, genes involved in metal transport (feoA, mntH, sirA), anaerobic metabolism genes (adhE, pflA, nrdDG) and a large number of virulence factors (lukSF, lukAB, nuc, gehB, norB, chs, scn and esxA). We show that ArlR directly activates expression of mgrA and identify a probable ArlR‐binding site (TTTTCTCAT‐N4‐TTTTAATAA). A highly similar sequence is also found in the spx P2 promoter, which was recently shown to be regulated by ArlRS. We also demonstrate that ArlS has kinase activity toward ArlR in vitro, although it has slower kinetics than other similar histidine kinases.
Dysbiosis Modulates Ocular Surface Inflammatory Response to Liposaccharide

Purpose The purpose of this study was to investigate the inflammatory response of cornea and conjunctiva to topically applied lipopolysaccharide (LPS) in mice with and without antibiotic (antibiotic cocktail, ABX) induced dysbiosis. Methods Dysbiosis was induced by oral antibiotics for 14 days in a group of conventional female C57BL/6J (B6) mice. 16S rRNA sequencing investigated microbiome composition. Intestinal microbiome differences were assessed using 16S rRNA sequencing of fecal pellet DNA. Blood was collected after euthanasia. CD86 expression in draining nodes was examined by flow cytometry. At day 15, a single dose of LPS or vehicle was topically applied to ABX and naïve mice. Corneal epithelium and conjunctiva were obtained after 4 hours and processed for gene expression analysis. A separate group of germ-free (GF) B6 mice was also topically challenged with LPS. Results Antibiotic treatment significantly decreased intestinal diversity and increased serum levels of LPS. This was accompanied by a significant increase in CD86+MHC II+CD11c+CD11b+ cells in draining nodes. Compared to vehicle, topically applied LPS increased IL-1β, TNF-α, and CXCL10 mRNA transcripts in cornea and IL-1β, TNF-α, and CXCL10 in the conjunctiva in conventional and antibiotic-treated groups. However, there was higher TNF-α, CXCL10, and IL-12 expression in the cornea of LPS-treated ABX mice compared to LPS-treated mice with intact microbiota. LPS stimulation on GF conjunctiva mirrored the results in ABX mice, although greater IL-12 and IFN-γ expression was observed in GF conjunctiva compared to conventional LPS-treated mice. Conclusions Acute depletion of commensals through antibiotics or germ-free environment worsens the inflammatory response to LPS.
Differentiating Preschool Children with Conduct Problems and Callous-Unemotional Behaviors through Emotion Regulation and Executive Functioning

ABSTRACT Callous-unemotional (CU) traits are important characteristics for identifying severe patterns of conduct problems (CP). The current study focused on (a) identifying subgroups of young children displaying a combination of CP and CU behaviors and (b) examining the extent to which executive functioning (EF) and emotion regulation (ER) are associated with CU behaviors. Participants included 249 preschoolers (N = 249, 78% boys, M age = 4.95 years; 81% Latino/Hispanic) referred to treatment because of externalizing behavior problems. CU behaviors and CP were measured via a combination of teacher/parent rating scales. A multimethod approach was used to measure EF and ER including parent/teacher rating scales, neuropsychological, and observational tasks. Poorer ER as rated by parents/teachers and observed was associated with greater levels of CU behaviors. Latent profile analyses identified three subgroups of children displaying (a) low CU/low CP, (b) moderate CU/moderate CP, and (c) high CU/high CP. Children in the high CU/high-CP group were rated as having significantly poorer rated ER compared to all other groups and poorer observed ER compared to the low-CU/low-CP group. Exploratory analyses found that children in the high-CU/high-CP group displayed marginally lower levels of rated ER but significantly better EF performance on standardized neuropsychological tasks compared to children in a low-CU/high-CP group.Children with higher levels of reported CU behaviors and CP display poorer ER yet may display relatively better EF performance compared to children with lower levels of CU behaviors and CP.
External validation of the HANDOC score – high sensitivity to identify patients with non-beta-haemolytic streptococcal endocarditis

Abstract Background: Invasive infections with non-beta-haemolytic streptococci (NBHS) is quite common and presents the clinicians with difficulties regarding which patients are at risk for infective endocarditis (IE). The HANDOC score was developed to identify patients with NBHS bacteraemia who are at low risk of IE. This study was conducted to validate HANDOC in an external cohort. Methods: Patients with NBHS in blood cultures between March and September 2016 in a Danish centre were included as part of an on-going study. Patient characteristics were collected to classify bacteria according to Dukés criteria and the components of the HANDOC score were collected retrospectively from the patients’ medical records. Results: 68 patients were included in the cohort, of which 16 fulfilled Dukés criteria for IE. All patients with IE (16 of 16) had a HANDOC score above the predefined cut-off. Cases of IE were found in patients with. Streptococcus mitis, Streptococcus bovis, Streptococcus mutans, Streptococcus anginosus, and Streptococcus sanguinis group streptococci. The HANDOC score thus had a sensitivity of 100% and a specificity of 62% in this cohort. Conclusions: HANDOC has a sensitivity of 100% and a relatively high specificity (62%) also in a prospectively enrolled cohort of patients from another country than its origin. This indicates that HANDOC can be implemented in clinical practice to identify patients with a low risk of IE in whom echocardiography can be omitted.
Treadmill Running in Established Phase Arthritis Inhibits Joint Destruction in Rat Rheumatoid Arthritis Models

Exercise therapy inhibits joint destruction by suppressing pro-inflammatory cytokines. The efficacy of pharmacotherapy for rheumatoid arthritis differs depending on the phase of the disease, but that of exercise therapy for each phase is unknown. We assessed the differences in the efficacy of treadmill running on rheumatoid arthritis at various phases, using rat rheumatoid arthritis models. Rats with collagen-induced arthritis were used as rheumatoid arthritis models, and the phase after immunization was divided as pre-arthritis and established phases. Histologically, the groups with forced treadmill running in the established phase had significantly inhibited joint destruction compared with the other groups. The group with forced treadmill running in only the established phase had significantly better bone morphometry and reduced expression of connexin 43 and tumor necrosis factor α in the synovial membranes compared with the no treadmill group. Furthermore, few cells were positive for cathepsin K immunostaining in the groups with forced treadmill running in the established phase. Our results suggest that the efficacy of exercise therapy may differ depending on rheumatoid arthritis disease activity. Active exercise during phases of decreased disease activity may effectively inhibit arthritis and joint destruction.
Is Disgust a “Conservative” Emotion?

Extant political–psychological research has identified stable, context-independent differences between conservatives and liberals in a wide range of preferences and psychological processes. One consistent finding is that conservatives show higher disgust sensitivity than liberals. This finding, however, is predominantly based on assessments of disgust to specific elicitors, which confound individuals’ sensitivity and propensity to the experience of disgust with the extent to which they find specific elicitors disgusting. Across five studies, we vary specific elicitors of disgust, showing that the relations between political orientation and disgust sensitivity depend on the specific set of elicitors used. We also show that disgust sensitivity is not associated with political orientation when measured with an elicitor-unspecific scale. Taken together, our findings suggest that the differences between conservatives and liberals in disgust sensitivity are context dependent rather than a stable personality difference. Broader theoretical implications are discussed.
Novel heterozygous sequence variant in the GLI1 underlies postaxial polydactyly

Polydactyly is one of the most common congenital abnormal phenotype of autopod, which is characterized by extra supernumerary digit in hands/feet with or without well‐developed bony structure within the digits. Preaxial polydactyly (PPD), postaxial polydactyly (PAP), and meso‐axial (central) polydactyly are three different isoforms of polydactyly. Genetically, at least 10 genes have been identified causing nonsyndromic polydactyly. In the present study, we have investigated a large family segregating autosomal dominant form of nonsyndromic polydactyly. Whole exome sequencing followed by Sanger sequencing revealed a novel heterozygous missense variant (NM_005269.3; c.1064C>A; p.(Thr355Asn) in the gene GLI1 segregating with the disease phenotype within the family. This study presents first familial case of autosomal dominant form of polydactyly caused by the GLI1 variant.
Technological and Therapeutic Advances in Advanced Small Cell Lung Cancer

Small cell lung cancer (SCLC) accounts for approximately 10–15% of all lung cancers. The prognosis is poor with median survival in the advanced stage remaining at around 12 months. Despite applying every known therapeutic approach, no major breakthrough has improved the overall survival in the last 30 years. Historically, experiments performed on conventional cell lines may have limitations of not accurately reflecting the complex biological and genomic heterogeneity of this disease. However, additional knowledge gained from recently developed genetically engineered mouse models (GEMMs) and patient derived xenografts (PDXs) have made encouraging inroads. Whole genome sequencing (WGS) data reveals a high mutational burden and a number of genetic alterations but low frequency of targetable mutations. Despite several failures, considerable therapeutic opportunities have recently emerged. Potentially promising therapies include those targeting DNA damage repair, stem cell/renewal and drug resistant mechanisms. Modest success has also been achieved with immune checkpoint inhibitors while therapeutic exploration of various other components of the immune system is underway. However, the complex heterogeneities reflect the need for accurate bio-markers to translate novel discoveries into clinical benefit. Additionally, the molecular mechanisms that differentiate chemo-sensitive from chemo-refractory disease remain unknown. Obtaining reliable tumour samples by utilising novel techniques such as endobronchial ultrasound guided needle aspiration or adopting to liquid biopsies are becoming popular. This review will focus on recent technological and therapeutic advancements to surmount this recalcitrant disease.
Children of the Nineties

A survey to assess factors, especially those in the environment, which influence child health and development is shortly to be started within the South West region. This study will start during pregnancy and involve both the mother and her partner as well as the child. Data will be collected on environmental exposures, and psychosocial aspects of the family home. Biological samples will also be kept and stored as a means of identifying pollutants inter alia, and to assess their influence on the fetus/infant. The children will be followed up to the age of 7 when they will receive a full educational, psychological and medical examination. Follow up of the outcome of pregnancy and the development of the child will help identify ways in which the environment influences child health and development.
Productive Infection of Mouse Mammary Glands and Human Mammary Epithelial Cells by Zika Virus

Zika virus (ZIKV) belongs to the large category of arboviruses. Surprisingly, several human-to-human transmissions of ZIKV have been notified, either following sexual intercourse or from the mother to fetus during pregnancy. Importantly, high viral loads have been detected in the human breast milk of infected mothers, and the existence of breastfeeding as a new mode of mother-to-child transmission of ZIKV was recently hypothesized. However, the maternal origin of infectious particles in breast milk is currently unknown. Here, we show that ZIKV disseminates to the mammary glands of infected mice after both systemic and local exposure with differential kinetics. Ex vivo, we demonstrate that primary human mammary epithelial cells were sensitive and permissive to ZIKV infection in this study. Moreover, by using in vitro models, we prove that mammary luminal- and myoepithelial-phenotype cell lines are both able to produce important virus progeny after ZIKV exposure. Our data suggest that the dissemination of ZIKV to the mammary glands and subsequent infection of the mammary epithelium could be one mechanism of viral excretion in human breast milk.
Chondroprotective effects of 4-methylumbelliferone and hyaluronan synthase-2 overexpression involve changes in chondrocyte energy metabolism

Hyaluronan is a critical component of articular cartilage and partially helps retain aggrecan within the extracellular matrix of this tissue. During osteoarthritis, hyaluronan and aggrecan loss are an early sign of tissue damage. However, our recent attempts to mimic hyaluronan loss with the hyaluronan inhibitor 4-methylumbelliferone (4MU) did not exacerbate arthritis-like features of in vitro models of arthritis, but surprisingly, caused the reverse (i.e. provided potent chondroprotection). Moreover, the protective effects of 4MU did not depend on its role as a hyaluronan inhibitor. To understand the molecular mechanism in 4MU-mediated chondroprotection, we considered recent studies suggesting that shifts in intracellular UDP-hexose pools promote changes in metabolism. To determine whether such metabolic shifts are associated with the mechanism of 4MU-mediated pro-catabolic inhibition, using molecular and metabolomics approaches, we examined whether bovine and human chondrocytes exhibit changes in the contribution of glycolysis and mitochondrial respiration to ATP production rates as well as in other factors that respond to or might drive these changes. Overexpression of either HA synthase-2 or 4MU effectively reduced dependence on glycolysis in chondrocytes, especially enhancing glycolysis use by interleukin-1β (IL1β)-activated chondrocytes. The reduction in glycolysis secondarily enhanced mitochondrial respiration in chondrocytes, which, in turn, rescued phospho-AMP–activated protein kinase (AMPK) levels in the activated chondrocytes. Other glycolysis inhibitors, unrelated to hyaluronan biosynthesis, namely 2-deoxyglucose and dichloroacetate, caused metabolic changes in chondrocytes equivalent to those elicited by 4MU and similarly protected both chondrocytes and cartilage explants. These results suggest that fluxes in UDP-hexoses alter metabolic energy pathways in cartilage.
Identifying High-Impact and Managing Low-Impact Assessment Practices

Those in pharmacy education who are tasked with assessment may be overwhelmed by deadlines, data collection, and reporting, leaving little time to pause and examine the effectiveness of their efforts. However, assessment practices must be evaluated for their impact, including their ability to answer important questions, use resources effectively, and contribute to meaningful educational change. Often assessments are implemented, but then attention is diverted to another assessment before the data from the former assessment can be fully interpreted or used. To maximize the impact of assessment practices, tough and uncomfortable decisions may need to be made. In this paper, we suggest an approach for examining and making decisions about assessment activities and provide guidance on building high-impact assessment practices, evolving or “sunsetting” low-impact assessment practices, and managing mandated assessment.
microRNA‐132 inhibits cardiomyocyte apoptosis and myocardial remodeling in myocardial infarction by targeting IL‐1β

The patients suffering from myocardial infarction (MI) undergo cardiac remodeling with the features of expanded myocardial infarct size and dilated left ventricle. Multiple microRNAs (miRNAs) are emerged as crucial modulators to participate in the remodeling process. This study is mainly intended to clarify the regulatory mechanism of miR‐132 in the MI‐induced myocardial remodeling. miR‐132 low expression, while interleukin‐1β (IL‐1β) high expression was determined in MI by reverse‐transcription quantitative polymerase chain reaction and ELISA assays. MI rats showed decreased cardiac function and increased cardiomyocyte apoptosis. Moreover, miR‐132 and IL‐1β levels were altered in cardiomyocytes to explore their role in MI, with levels of proapoptotic or antiapoptotic proteins in MI together with cardiac function indexes observed. In addition, upregulation of miR‐132, decreased levels of Bax and Cleaved Caspase‐3, increased left ventricular ejection fraction, left ventricular fractional shortening, the maximum rate of rise or decrease of left ventricular pressure (±dp/dtmax), and Bcl‐2 level, which could be reversed by overexpressing IL‐1β. All in all, miR‐132 inhibits cardiomyocyte apoptosis so as to ameliorate myocardial remodeling in rats with MI through IL‐1β downregulation. Thus, miR‐132 is a potential candidate for the MI treatment.
Physiology of the Carotid Body: From Molecules to Disease.

The carotid body (CB) is an arterial chemoreceptor organ located in the carotid bifurcation and has a well-recognized role in cardiorespiratory regulation. The CB contains neurosecretory sensory cells (glomus cells), which release transmitters in response to hypoxia, hypercapnia, and acidemia to activate afferent sensory fibers terminating in the respiratory and autonomic brainstem centers. Knowledge of the physiology of the CB has progressed enormously in recent years. Herein we review advances concerning the organization and function of the cellular elements of the CB, with emphasis on the molecular mechanisms of acute oxygen sensing by glomus cells. We introduce the modern view of the CB as a multimodal integrated metabolic sensor and describe the properties of the CB stem cell niche, which support CB growth during acclimatization to chronic hypoxia. Finally, we discuss the increasing medical relevance of CB dysfunction and its potential impact on the mechanisms of disease. Expected final online publication date for the Annual Review of Physiology, Volume 82 is February 10, 2020. Please see http://www.annualreviews. org/page/journal/pubdates for revised estimates.
Prognostic performance of pancreatic stone protein in critically ill patients with sepsis.

Aim: To assess the prognostic value for 28-day mortality of PSP in critically ill patients with sepsis. Material & methods: 122 consecutive patients with sepsis were enrolled in this study. Blood samples were collected on admission and day 2. Results: On admission, the combination of PSP and lactate achieved an area under the receiver operating characteristic (AUC-ROC) of 0.796, similar to SOFA score alone (AUC-ROC: 0.826). On day 2, PSP was the biomarker with the highest performance (AUC-ROC: 0.844), although lower (p = 0.041) than SOFA score (AUC-ROC: 0.923). Conclusion: The combination of PSP and lactate and PSP alone, on day 2, have a good performance for prognosis of 28-day mortality and could help to identify patients who may benefit most from tailored intensive care unit management.