Miracle-dz/UniFAR-FTUs huggingface dataset:
Circulating and tissue angiotensin systems.

Angiotensin has many different actions, most of which relate, either directly or indirectly, to the regulation of blood pressure, fluid, and electrolyte homeostasis (1, 2). In addition to potent vasoconstrictor effects, actions ofangiotensin on vasculature include the stimulation ofprostaglandin release (3), the modulation of angiotensin receptor number (4), and the stimulation of angiogenesis (5). Angiotensin also has important actions on the central and peripheral nervous systems, the adrenal, kidney, intestine, and heart (6-1 1). Given these multiple diverse actions of angiotensin, two important questions are (a) which of these actions represent normal physiological events, and (b) whether such actions may assume a pathogenic role. These questions have recently been placed in sharper focus by the clinical application of inhibitors of the renin-angiotensin system (RAS),' and in particular, the use of converting enzyme inhibitors (CEIs) for the treatment of hypertension. Any attempt to answer these questions requires an accurate concept ofthe RAS. The purpose of this review is to discuss new concepts concerning angiotensin production by the circulating RAS, how these relate to angiotensin production within tissues, and the possible mechanisms by which CEIs lower blood pressure. The study of tissue angiotensin systems is still at an early stage. In this review I have attempted to synthesize a coherent model of the interaction between the circulating and tissue angiotensin systems, which might assist in the interpretation of new developments in this area.
On the Close Relatedness of Two Rice-Parasitic Root-Knot Nematode Species and the Recent Expansion of Meloidogyne graminicola in Southeast Asia

Meloidogyne graminicola is a facultative meiotic parthenogenetic root-knot nematode (RKN) that seriously threatens agriculture worldwide. We have little understanding of its origin, genomic structure, and intraspecific diversity. Such information would offer better knowledge of how this nematode successfully damages rice in many different environments. Previous studies on nuclear ribosomal DNA (nrDNA) suggested a close phylogenetic relationship between M. graminicola and Meloidogyne oryzae, despite their different modes of reproduction and geographical distribution. In order to clarify the evolutionary history of these two species and explore their molecular intraspecific diversity, we sequenced the genome of 12 M. graminicola isolates, representing populations of worldwide origins, and two South American isolates of M. oryzae. k-mer analysis of their nuclear genome and the detection of divergent homologous genomic sequences indicate that both species show a high proportion of heterozygous sites (ca. 1–2%), which had never been previously reported in facultative meiotic parthenogenetic RKNs. These analyses also point to a distinct ploidy level in each species, compatible with a diploid M. graminicola and a triploid M. oryzae. Phylogenetic analyses of mitochondrial genomes and three nuclear genomic sequences confirm close relationships between these two species, with M. graminicola being a putative parent of M. oryzae. In addition, comparative mitogenomics of those 12 M. graminicola isolates with a Chinese published isolate reveal only 15 polymorphisms that are phylogenetically non-informative. Eight mitotypes are distinguished, the most common one being shared by distant populations from Asia and America. This low intraspecific diversity, coupled with a lack of phylogeographic signal, suggests a recent worldwide expansion of M. graminicola.
Longitudinal evaluation of immunological responses to allergen‐specific immunotherapy in horses with IgE associated dermatological disease, a pilot study

BACKGROUND The long-term effects of allergen specific immunotherapy (ASIT) on concentrations of circulating immunoglobulin E (IgE) and immunoglobulin G (IgG) in horses have not been reported. OBJECTIVES To document changes in clinical severity of horses with atopic dermatitis (AD) and to monitor allergen-specific IgE and IgG concentrations during a two-year course of ASIT. ANIMALS Nineteen client-owned horses with a conditional diagnosis of AD. METHODS AND MATERIALS Three ASIT groups were randomly assigned based upon results obtained by either intradermal testing (IDT) for regional allergens (n = 7); enzyme-linked immunosorbent assay (ELISA) for specific IgE (n = 6); or a composite of results from both tests (n = 6). Serum concentrations of IgE and IgG specific for allergens included in ASIT were measured at time zero and at four-month intervals. A visual analog scale (VAS) was used to record severity of clinical signs at times zero, 12 and 24 months. RESULTS Positive correlations were documented between IgE and both immediate and delayed IDT results (P < 0.00001), and between immediate IDT and IgG results (P = 0.003). Specific IgE in sera decreased significantly (P < 0.05) for allergens that were included in ASIT, whereas IgG increased. Across all horses, the mean VAS score decreased by 1.2 units [95% CI: 1.28, 1.14; (P < 0.0001)] during each 12-month period of ASIT therapy. Improvement in clinical signs was noted in 76.5% of the horses following 12 months of ASIT and in 82% after 24 months on ASIT. CONCLUSIONS AND CLINICAL IMPORTANCE In this pilot study, ASIT in horses with AD provided significant clinical benefit associated with a concomitant reduction of allergen-specific IgE and elevation of IgG.
Antibody-suppressor CD8+ T cells require CXCR5.

BACKGROUND We previously reported the novel activity of alloprimed CD8 T cells that suppress post transplant alloantibody production. The purpose of the current study is to investigate the expression and role of CXCR5 on antibody-suppressor CD8 T cell function. METHODS C57BL/6 mice were transplanted with FVB/N hepatocytes. Alloprimed CD8 T cells were retrieved on day 7 from hepatocyte transplant recipients. Unsorted or flow-sorted (CXCR5CXCR3 and CXCR3CXCR5) alloprimed CD8 T cell subsets were analyzed for in vitro cytotoxicity and capacity to inhibit in vivo alloantibody production following adoptive transfer into C57BL/6 or high alloantibody-producing CD8 KO hepatocyte transplant recipients. Alloantibody titer was assessed in CD8 KO mice reconstituted with naïve CD8 T cells retrieved from C57BL/6, CXCR5 KO or CXCR3 KO mice. Antibody suppression by OVA-primed monoclonal OT-I CXCR5 or CXCR3 CD8 T cell subsets was also investigated. RESULTS Alloprimed CXCR5CXCR3CD8 T cells mediated in vitro cytotoxicity of alloprimed "self" B cells while CXCR3CXCR5CD8 T cells did not. Only flow-sorted alloprimed CXCR5CXCR3CD8 T cells (not flow-sorted alloprimed CXCR3CXCR5CD8 T cells) suppressed alloantibody production and enhanced graft survival when transferred into transplant recipients. Unlike CD8 T cells from wild-type or CXCR3 KO mice, CD8 T cells from CXCR5 KO mice do not develop alloantibody-suppressor function. Similarly, only flow-sorted CXCR5CXCR3 (and not CXCR3CXCR5) OVA-primed OT-I CD8 T cells mediated in vivo suppression of anti-OVA antibody production. CONCLUSION These data support the conclusion that expression of CXCR5 by antigen-primed CD8 T cells is critical for the function of antibody-suppressor CD8 T cells.
Diagnosis, Treatment, and Long-Term Management of Kawasaki Disease: A Scientific Statement for Health Professionals From the American Heart Association

Background: Kawasaki disease is an acute vasculitis of childhood that leads to coronary artery aneurysms in ≈25% of untreated cases. It has been reported worldwide and is the leading cause of acquired heart disease in children in developed countries. Methods and Results: To revise the previous American Heart Association guidelines, a multidisciplinary writing group of experts was convened to review and appraise available evidence and practice-based opinion, as well as to provide updated recommendations for diagnosis, treatment of the acute illness, and long-term management. Although the cause remains unknown, discussion sections highlight new insights into the epidemiology, genetics, pathogenesis, pathology, natural history, and long-term outcomes. Prompt diagnosis is essential, and an updated algorithm defines supplemental information to be used to assist the diagnosis when classic clinical criteria are incomplete. Although intravenous immune globulin is the mainstay of initial treatment, the role for additional primary therapy in selected patients is discussed. Approximately 10% to 20% of patients do not respond to initial intravenous immune globulin, and recommendations for additional therapies are provided. Careful initial management of evolving coronary artery abnormalities is essential, necessitating an increased frequency of assessments and escalation of thromboprophylaxis. Risk stratification for long-term management is based primarily on maximal coronary artery luminal dimensions, normalized as Z scores, and is calibrated to both past and current involvement. Patients with aneurysms require life-long and uninterrupted cardiology follow-up. Conclusions: These recommendations provide updated and best evidence-based guidance to healthcare providers who diagnose and manage Kawasaki disease, but clinical decision making should be individualized to specific patient circumstances.
Effective Factors for Development of Gerontological Nursing Competence: A Qualitative Study.

BACKGROUND Many nurses working in hospitals are not prepared to provide appropriate care for older people. This qualitative study aimed to identify factors influencing the development of gerontological nursing competence in Iranian hospitals. METHOD Twenty-six participants (nine nurses, 12 nurse managers, four clinical instructors, one physician) who worked in four teaching hospitals and nursing schools were interviewed by semistructured interview method. Conventional content analysis was used. RESULTS Two main categories emerged from the data: (a) management factors with the subcategories of meritocracy in elderly nursing, leadership style of nursing managers, educational system, the quality of working life, and performance management; (b) organizational factors with the subcategories of organizational learning, and organizational support. CONCLUSION These findings can help nurse managers and clinical instructors identify, develop, and implement strategies for further development of gerontological nursing competence. [J Contin Educ Nurs. 2019;50(3):127-133. ].
iTRAQ‐based proteomic analysis of human umbilical vein endothelial cells with platelet endothelial aggregation receptor‐1 knockdown

The disorders of hemostasis and coagulation were believed to be the main contributors to the pathogenesis of pulmonary thromboembolism (PTE), and platelets are the basic factors regulating hemostasis and coagulation and play important roles in the process of thrombosis. This study investigated the proteome of human umbilical vein endothelial cells (HUVECs) with platelet endothelial aggregation receptor‐1 (PEAR1) knockdown using the isobaric tags for relative and absolute quantitation (iTRAQ) method and analyzed the role of differential abundance proteins (DAPs) in the regulation of platelets aggregation. Our results showed that the conditioned media‐culturing HUVECs with PEAR1 knockdown partially suppressed the adenosine diphosphate (ADP)‐induced platelet aggregation. The proteomics analysis was performed by using the iTRAQ technique, and a total of 215 DAPs (124 protein was upregulated and 91 protein were downregulated) were identified. The Gene Ontology (GO) enrichment analysis showed that proteins related to platelet α granule, adenosine triphosphate metabolic process, and endocytosis were significantly enriched. Further, the Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis also identified the significant enrichment of endocytosis‐related pathways. The real‐time polymerase chain reaction assay confirmed that the expression of P2Y12, mitochondrial carrier 2, NADH dehydrogenase (ubiquinone) iron‐sulfur protein 3, and ubiquinol‐cytochrome c reductase hinge protein are significantly downregulated in the HUVECs with PEAR1 knockdown. In conclusion, our in vitro results implicated that DAPs induced by PEAR1 knockdown might contribute to the platelet aggregation. Proteomic studies by employing GO enrichment and KEGG pathway analysis suggested that the potential effects of DAPs on platelet aggregation may be linked to the balance of ADP synthesis or degradation in mitochondria.
High $k_{t}^{2}$ Exceeding 6.4% Through Metal Frames in Aluminum Nitride 2-D Mode Resonators

This work describes a new method to enhance the electromechanical coupling coefficient (<inline-formula> <tex-math notation="LaTeX">$k_{t}^{2}$ </tex-math></inline-formula>) of 2-D mode resonators (2DMRs). This approach exploits the multimodal excitation of different Lamb waves to achieve a quasi-uniform vertical displacement distribution in the electrode regions of 2DMRs. To do so, the 2DMRs reported in this work rely on the use of metal frame structures placed at the edges of each metal strip forming the electrode gratings. To demonstrate the effectiveness of this new technique in enhancing <inline-formula> <tex-math notation="LaTeX">$k_{t}^{2}$ </tex-math></inline-formula>, we report the design and simulated performance through the finite-element methods of a 2.5-GHz 2DMR using metal frames. Our analysis proves that this device can simultaneously exhibit high <inline-formula> <tex-math notation="LaTeX">$k_{t}^{2}$ </tex-math></inline-formula> in excess of 6.4% and wide lithographic frequency tunability in excess of 10%, thus approaching the reported performance of aluminum nitride (AlN) film bulk acoustic resonators (FBARs) operating within the same frequency range.
Comment on Cheung and Moses. Gestational Diabetes Mellitus: Is It Time to Reconsider the Diagnostic Criteria? Diabetes Care 2018;41:1337–1338

While it may be unconventional to comment on a Commentary, emphasis on some of the points raised by Cheung and Moses (1) as well as the addition of a few others seems indicated. The Hyperglycemia and Adverse Pregnancy Outcome (HAPO) study, which combined data from 15 medical centers on five continents, created a large database of glucose tolerance test (GTT) results of pregnant women representing a diversity of racial and ethnic groups. Their combined data demonstrated a near-linear positive association between maternal glucose levels and selected adverse pregnancy outcomes (2). Given this observation, one may reasonably infer that threshold values defining gestational diabetes mellitus (GDM) derived from these data will correctly identify for …
A faster PISTOL for 1H MR‐based quantitative tissue oximetry

Quantitative mapping of oxygen tension (pO2), noninvasively, could potentially be beneficial in cancer and stroke therapy for monitoring therapy and predicting response to certain therapies. Intracellular pO2 measurements may also prove useful in tracking the health of labeled cells and understanding the dynamics of cell therapy in vivo. Proton Imaging of Siloxanes to map Tissue Oxygenation Levels (PISTOL) is a relatively new oximetry technique that measures the T1 of administered siloxanes such as hexamethyldisiloxane (HMDSO), to map the tissue pO2 at various locations with a temporal resolution of 3.5 minutes. We have now developed a siloxane‐selective Look‐Locker imaging sequence equipped with an echo planar imaging (EPI) readout to accelerate PISTOL acquisitions. The new tissue oximetry sequence, referred to as PISTOL‐LL, enables the mapping of HMDSO T1, and hence tissue pO2 in under one minute. PISTOL‐LL was tested and compared with PISTOL in vitro and in vivo. Both sequences were used to record dynamic changes in pO2 of the rat thigh muscle (healthy Fischer rats, n = 6), and showed similar results (P > 0.05) as the other, with each sequence reporting a significant increase in pO2 (P < 0.05) under hyperoxia compared with steady state normoxia. This study demonstrates the ability of the new sequence in rapidly and accurately mapping the pO2 changes and accelerating quantitative 1H MR tissue oximetry by approximately 4‐fold. The faster PISTOL‐LL technique could enable dynamic 1H oximetry with higher temporal resolution for assesing tissue oxygentation and tracking the health of transplanted cells labeled with siloxane‐based probes. With minor modifications, this sequence can be useful for 19F applications as well.
Cancer risk following post‐transplant lymphoproliferative disorders in solid organ transplant recipients

nucci, R. , Pileri, S. & Nicoletti, I. (2009) Altered nucleophosmin transport in acute myeloid leukaemia with mutated NPM1: molecular basis and clinical implications. Leukemia, 23, 1731–1743. Falini, B. , Martelli, M.P., Bolli, N. , Sportoletti, P., Liso, A. , Tiacci, E. & Haferlach, T. (2011) Acute myeloid leukemia with mutated nucleophosmin (NPM1): is it a distinct entity? Blood, 117, 1109–1120. Falini, B. , Brunetti, L. & Martelli, M.F. (2015) Dactinomycin in NPM1-mutated acute myeloid leukemia. New England Journal of Medicine, 373, 1178–1180. Grummitt, C.G. , Townsley, F.M. , Johnson, C.M. , Warren, A.J. & Bycroft, M. (2008) Structural consequences of nucleophosmin mutations in acute myeloid leukemia. The Journal of Biological Chemistry, 283, 23326–23332.
Calycosin Ameliorates Diabetes-Induced Renal Inflammation via the NF-κB Pathway In Vitro and In Vivo

Background Diabetic nephropathy (DN), which is one of the primary causes of end-stage renal disease (ESRD), is increasingly diagnosed in patients due to the continuous increase in the prevalence of diabetic mellitus (DM). Astragali Radix, a traditional Chinese herb, is widely administrated to ameliorate the symptoms of diabetes and diabetic nephropathy, but its mechanism is still not yet fully defined. Calycosin (C16H12O5) is the major active component of Astragali Radix. In this study, we analyzed the role of calycosin in diabetic nephropathy and explored its underlying mechanism. Material/Methods Cell activation, inflammatory cytokines expression and secretion, and protein levels were analyzed in cultured mouse tubular epithelial cells (mTEC). db/db mice were intraperitoneally injected with 10 mg/(kg·d) calycosin or control saline for 4 weeks, followed by analysis of structure injury, inflammation, and NF-κB signaling activity. Results Our results indicated that TNF-α and IL-1β were significantly induced by advanced glycation end-products (AGEs), but calycosin remarkably reduced the expression of TNF-α and IL-1β in the cultured mouse tubular epithelial cells (mTEC). Calycosin effectively alleviated kidney injury in diabetic kidneys of db/db mice during the progression of diabetic renal injury, indicated by the reduction of histological injury and immunohistochemical of inflammatory cytokines. Mechanistically, we identified calycosin inhibited diabetes-induced inflammation in kidneys by suppressing the phosphorylation of IKBα and NF-κB p65 in vitro and in vivo. Conclusions Calycosin significantly ameliorated diabetes-induced renal inflammation in diabetic renal injury by inhibition of the NF-κB-dependent signaling pathway in vivo and in vitro.
Implementation and Evaluation of a 50 kHz, $28\mu\mathrm{s}$ Motion-to-Pose Latency Head Tracking Instrument

This paper presents the implementation and evaluation of a 50,000-pose-sample-per-second, 6-degree-of-freedom optical head tracking instrument with motion-to-pose latency of 28μs and dynamic precision of 1-2 arcminutes. The instrument uses high-intensity infrared emitters and two duo-lateral photodiode-based optical sensors to triangulate pose. This instrument serves two purposes: it is the first step towards the requisite head tracking component in sub- 100μs motion-to-photon latency optical see-through augmented reality (OST AR) head-mounted display (HMD) systems; and it enables new avenues of research into human visual perception - including measuring the thresholds for perceptible real-virtual displacement during head rotation and other human research requiring high-sample-rate motion tracking. The instrument's tracking volume is limited to about 120×120×250 but allows for the full range of natural head rotation and is sufficient for research involving seated users. We discuss how the instrument's tracking volume is scalable in multiple ways and some of the trade-offs involved therein. Finally, we introduce a novel laser-pointer-based measurement technique for assessing the instrument's tracking latency and repeatability. We show that the instrument's motion-to-pose latency is 28μs and that it is repeatable within 1-2 arcminutes at mean rotational velocities (yaw) in excess of 500°/sec.
Phosphodiesterase beta is the master regulator of cAMP signalling during malaria parasite invasion

Cyclic nucleotide signalling is a major regulator of malaria parasite differentiation. Phosphodiesterase (PDE) enzymes are known to control cyclic GMP (cGMP) levels in the parasite, but the mechanisms by which cyclic AMP (cAMP) is regulated remain enigmatic. Here, we demonstrate that Plasmodium falciparum phosphodiesterase β (PDEβ) hydrolyses both cAMP and cGMP and is essential for blood stage viability. Conditional gene disruption causes a profound reduction in invasion of erythrocytes and rapid death of those merozoites that invade. We show that this dual phenotype results from elevated cAMP levels and hyperactivation of the cAMP-dependent protein kinase (PKA). Phosphoproteomic analysis of PDEβ-null parasites reveals a >2-fold increase in phosphorylation at over 200 phosphosites, more than half of which conform to a PKA substrate consensus sequence. We conclude that PDEβ plays a critical role in governing correct temporal activation of PKA required for erythrocyte invasion, whilst suppressing untimely PKA activation during early intra-erythrocytic development.
Proton Pump Inhibitors and Risk of Acute and Chronic Kidney Disease: A Retrospective Cohort Study

Proton pump inhibitors (PPIs) have been linked to acute kidney injury (AKI) and chronic kidney disease (CKD); however, current evidence has only been evaluated in a small number of studies with short follow‐up periods. This study examined the association between PPI use and risk of incident AKI and CKD in a large population‐based health maintenance organization (HMO) cohort.
Experimental modulation of mood by acoustic stimulation and its effect on exertional dyspnoea

We examined the interactions between acoustically driven mood modulation and dyspnoea. Following familiarisation, 18 healthy participants attended three experimental sessions on separate days performing two 5 min treadmill tests with a 30 min interval per session while listening to either a positive, negative or neutral set of standardised International Affective Digitised Sounds (IADS). Participants rated intensity and affective domains of dyspnoea during the first exercise test and mood during the second. Mood valence was significantly higher when listening to positive (mean (95% CI): 6.5 (5.9–7.2)) compared with negative sounds (3.6 (2.9–4.4); p<0.001). Dyspnoea intensity and affect were statistically significantly lower when listening to positive (2.4 (1.8–2.9) and 1.3 (0.7–1.9)) compared with negative IADS (3.2 (2.3–3.7), p=0.013 and 2.3 (1.3–3.3), p=0.009). These findings indicate that acoustically induced mood changes influence exertional dyspnoea.