Change in Diuretic Dose after Initiation of a SGLT2 Inhibitor in Patients with Heart Failure with Reduced Ejection Fraction

Study Purpose: To identify change in loop diuretic dose when initiating a SGLT2i in patients with HFrEF who are on a stable dose of loop diuretic in the outpatient settinghttps://jdc.jefferson.edu/pharmacyposters/1025/thumbnail.jp

GeoTriples: Transforming geospatial data into RDF graphs using R2RML and RML mappings

A lot of geospatial data has become available at no charge in many countries recently. Geospatial data that is currently made available by government agencies usually do not follow the linked data paradigm. In the few cases where government agencies do follow the linked data paradigm (e.g., Ordnance Survey in the United Kingdom), specialized scripts have been used for transforming geospatial data into RDF. In this paper we present the open source tool GeoTriples which generates and processes extended R2RML and RML mappings that transform geospatial data from many input formats into RDF. GeoTriples allows the transformation of geospatial data stored in raw files (shapefiles, CSV, KML, XML, GML and GeoJSON) and spatially-enabled RDBMS (PostGIS and MonetDB) into RDF graphs using well-known vocabularies like GeoSPARQL and stSPARQL, but without being tightly coupled to a specific vocabulary. GeoTriples has been developed in European projects LEO and Melodies and has been used to transform many geospatial data sources into linked data. We study the performance of GeoTriples experimentally using large publicly available geospatial datasets, and show that GeoTriples is very efficient and scalable especially when its mapping processor is implemented using Apache Hadoop

A Novel Role of Peripheral Corticotropin-Releasing Hormone (CRH) on Dermal Fibroblasts

Corticotropin-releasing hormone, or factor, (CRH or CRF) exerts important biological effects in multiple peripheral tissues via paracrine/autocrine actions. The aim of our study was to assess the effects of endogenous CRH in the biology of mouse and human skin fibroblasts, the primary cell type involved in wound healing. We show expression of CRH and its receptors in primary fibroblasts, and we demonstrate the functionality of fibroblast CRH receptors by induction of cAMP. Fibroblasts genetically deficient in Crh (Crh−/−) had higher proliferation and migration rates and compromised production of IL-6 and TGF-β1 compared to the wildtype (Crh+/+) cells. Human primary cultures of foreskin fibroblasts exposed to the CRF1 antagonist antalarmin recapitulated the findings in the Crh−/− cells, exhibiting altered proliferative and migratory behavior and suppressed production of IL-6. In conclusion, our findings show an important role of fibroblast-expressed CRH in the proliferation, migration, and cytokine production of these cells, processes associated with the skin response to injury. Our data suggest that the immunomodulatory effects of CRH may include an important, albeit not explored yet, role in epidermal tissue remodeling and regeneration and maintenance of tissue homeostasis

Effect of religiosity/spirituality and sense of coherence on depression within a rural population in Greece: the Spili III project

Background: Recent research has addressed the hypothesis that religiosity/spirituality and sense of coherence buffer the negative effects of stress on numerous health issues. The aim of the current study was to further this work by exploring potential links between psycho-social factors such as religiosity/ spirituality and sense of coherence with depression. Methods: A total of 220 subjects of the SPILI III cohort (1988-2012) attending a primary care setting in the town of Spili on rural Crete represented the target group. All participants underwent a standardized procedure. Validated questionnaires were used to evaluate sense of coherence, depression levels and religious and spiritual beliefs. A multiple linear regression analysis of the Beck Depression Inventory Scale (BDI) in relation to demographic characteristics, scores on the Royal Free Interview for Spiritual and Religious Beliefs scale (RFI-SRB) and Sense of Coherence scale (SOC) was used. Results: A significant inverse association was found between BDI and RFI-SRB scale (B-coef=-0.6999, p<0.001), as well as among BDI and SOC scale (B-coef=-0.556, p<0.001). Conclusions: The findings of the current observational study indicate that highly religious participants are less likely to score high in the depression scale. Furthermore, participants with high SOC scored significantly low in the BDI scale. Further research is required in order to explore the potential effect of SOC and religiosity/spirituality in mental health

Elucidating the Role of Ligand Engineering on Local and Macroscopic Charge‐Carrier Transport in NaBiS2 Nanocrystal Thin Films

Ternary chalcogenides have emerged as potential candidates for ultrathin photovoltaics, and NaBiS2 nanocrystals (NCs) have gained appeal because of their months-long phase-stability in air, high absorption coefficients >105 cm−1, and a pseudo-direct bandgap of 1.4 eV. However, previous investigations into NaBiS2 NCs used long-chain organic ligands separating individual NCs during synthesis, which severely limits macroscopic charge-carrier transport. In this work, these long-chain ligands are exchanged for short iodide-based ligands, allowing to understand the macroscopic charge-carrier transport properties of NaBiS2 and evaluate its photovoltaic potential in more depth. It is found that ligand exchange results in simultaneous improvements in intra-NC (microscopic) and inter-NC (macroscopic) mobilities, while charge-carrier localization still takes place, which places a fundamental limit on the transport lengths achievable. Despite this limitation, the high absorption coefficients enable ultrathin (55 nm thick) solar absorbers to be used in photovoltaic devices, which have peak external quantum efficiencies > 50%. In addition, temperature-dependent transient current measurements uncover a small activation energy barrier of 88 meV for ion migration, which accounts for the strongly hysteretic behavior of NaBiS2 photovoltaic devices. This work not only reveals how the charge-carrier transport properties of NaBiS2 NCs over several length and time scales are influenced by ligand engineering, but also unveils the facile ionic transport in this material, which limits the potential of NaBiS2 in photovoltaics. On the other hand, the discovery shows that there are opportunities to use this material in memristors, electrolytes, and other applications requiring ionic conduction

Comparative analysis of the human hepatic and adipose tissue transcriptomes during LPS-induced inflammation leads to the identification of differential biological pathways and candidate biomarkers

<p>Abstract</p> <p>Background</p> <p>Insulin resistance (IR) is accompanied by chronic low grade systemic inflammation, obesity, and deregulation of total body energy homeostasis. We induced inflammation in adipose and liver tissues <it>in vitro </it>in order to mimic inflammation <it>in vivo </it>with the aim to identify tissue-specific processes implicated in IR and to find biomarkers indicative for tissue-specific IR.</p> <p>Methods</p> <p>Human adipose and liver tissues were cultured in the absence or presence of LPS and DNA Microarray Technology was applied for their transcriptome analysis. Gene Ontology (GO), gene functional analysis, and prediction of genes encoding for secretome were performed using publicly available bioinformatics tools (DAVID, STRING, SecretomeP). The transcriptome data were validated by proteomics analysis of the inflamed adipose tissue secretome.</p> <p>Results</p> <p>LPS treatment significantly affected 667 and 483 genes in adipose and liver tissues respectively. The GO analysis revealed that during inflammation adipose tissue, compared to liver tissue, had more significantly upregulated genes, GO terms, and functional clusters related to inflammation and angiogenesis. The secretome prediction led to identification of 399 and 236 genes in adipose and liver tissue respectively. The secretomes of both tissues shared 66 genes and the remaining genes were the differential candidate biomarkers indicative for inflamed adipose or liver tissue. The transcriptome data of the inflamed adipose tissue secretome showed excellent correlation with the proteomics data.</p> <p>Conclusions</p> <p>The higher number of altered proinflammatory genes, GO processes, and genes encoding for secretome during inflammation in adipose tissue compared to liver tissue, suggests that adipose tissue is the major organ contributing to the development of systemic inflammation observed in IR. The identified tissue-specific functional clusters and biomarkers might be used in a strategy for the development of tissue-targeted treatment of insulin resistance in patients.</p

STAMINA: Bioinformatics Platform for Monitoring and Mitigating Pandemic Outbreaks

Data Availability Statement: All data driven applications used the our world in data COVID-19 datasets, complimented by proprietary datasets share by the STAMINA consortium.Copyright © 2022 by the authors. This paper presents the components and integrated outcome of a system that aims to achieve early detection, monitoring and mitigation of pandemic outbreaks. The architecture of the platform aims at providing a number of pandemic-response-related services, on a modular basis, that allows for the easy customization of the platform to address user’s needs per case. This customization is achieved through its ability to deploy only the necessary, loosely coupled services and tools for each case, and by providing a common authentication, data storage and data exchange infrastructure. This way, the platform can provide the necessary services without the burden of additional services that are not of use in the current deployment (e.g., predictive models for pathogens that are not endemic to the deployment area). All the decisions taken for the communication and integration of the tools that compose the platform adhere to this basic principle. The tools presented here as well as their integration is part of the project STAMINA.The paper presented is based on research undertaken as part of the European Commission-funded project STAMINA (Grant Agreement 883441)

Loss of Cannabinoid Receptor CB1 Induces Preterm Birth

Preterm birth accounting approximate 10% of pregnancies in women is a tremendous social, clinical and economic burden. However, its underlying causes remain largely unknown. Emerging evidence suggests that endocannabinoid signaling via cannabinoid receptor CB1 play critical roles in multiple early pregnancy events in both animals and humans. Since our previous studies demonstrated that loss of CB1 defers the normal implantation window in mice, we surmised that CB1 deficiency would influence parturition events.Exploiting mouse models with targeted deletion of Cnr1, Cnr2 and Ptgs1 encoding CB1, CB2 and cyclooxygenase-1, respectively, we examined consequences of CB1 or CB2 silencing on the onset of parturition. We observed that genetic or pharmacological inactivation of CB1, but not CB2, induced preterm labor in mice. Radioimmunoassay analysis of circulating levels of ovarian steroid hormones revealed that premature birth resulting from CB1 inactivation is correlated with altered progesterone/estrogen ratios prior to parturition. More strikingly, the phenotypic defects of prolonged pregnancy length and parturition failure in mice missing Ptgs1 were corrected by introducing CB1 deficiency into Ptgs1 null mice. In addition, loss of CB1 resulted in aberrant secretions of corticotrophin-releasing hormone and corticosterone during late gestation. The pathophysiological significance of this altered corticotrophin-releasing hormone-driven endocrine activity in the absence of CB1 was evident from our subsequent findings that a selective corticotrophin-releasing hormone antagonist was able to restore the normal parturition timing in Cnr1 deficient mice. In contrast, wild-type females receiving excessive levels of corticosterone induced preterm birth.CB1 deficiency altering normal progesterone and estrogen levels induces preterm birth in mice. This defect is independent of prostaglandins produced by cyclooxygenase-1. Moreover, CB1 inactivation resulted in aberrant corticotrophin-releasing hormone and corticosterone activities prior to parturition, suggesting that CB1 regulates labor by interacting with the corticotrophin-releasing hormone-driven endocrine axis

Amygdala inputs to prefrontal cortex guide behavior amid conflicting cues of reward and punishment

Orchestrating appropriate behavioral responses in the face of competing signals that predict either rewards or threats in the environment is crucial for survival. The basolateral nucleus of the amygdala (BLA) and prelimbic (PL) medial prefrontal cortex have been implicated in reward-seeking and fear-related responses, but how information flows between these reciprocally connected structures to coordinate behavior is unknown. We recorded neuronal activity from the BLA and PL while rats performed a task wherein competing shock- and sucrose-predictive cues were simultaneously presented. The correlated firing primarily displayed a BLA→PL directionality during the shock-associated cue. Furthermore, BLA neurons optogenetically identified as projecting to PL more accurately predicted behavioral responses during competition than unidentified BLA neurons. Finally photostimulation of the BLA→PL projection increased freezing, whereas both chemogenetic and optogenetic inhibition reduced freezing. Therefore, the BLA→PL circuit is critical in governing the selection of behavioral responses in the face of competing signals.National Institutes of Health (U.S.) (Award 1R25-MH092912-01)National Institute of Mental Health (U.S.) (Grant R01- MH102441-01)National Institutes of Health (U.S.) (Award DP2- DK-102256-01

GABA Receptors and the Pharmacology of Sleep

Current GABAergic sleep-promoting medications were developed pragmatically, without making use of the immense diversity of GABAA receptors. Pharmacogenetic experiments are leading to an understanding of the circuit mechanisms in the hypothalamus by which zolpidem and similar compounds induce sleep at α2βγ2-type GABAA receptors. Drugs acting at more selective receptor types, for example, at receptors containing the α2 and/or α3 subunits expressed in hypothalamic and brain stem areas, could in principle be useful as hypnotics/anxiolytics. A highly promising sleep-promoting drug, gaboxadol, which activates αβδ-type receptors failed in clinical trials. Thus, for the time being, drugs such as zolpidem, which work as positive allosteric modulators at GABAA receptors, continue to be some of the most effective compounds to treat primary insomnia