Miracle-dz/UniFAR-FTUs huggingface dataset:
Systemic effects of inhaled corticosteroids in children

Purpose of review Inhaled corticosteroids (ICS) are first-line therapy for persistent asthma in children. Major safety concerns about long-term ICS therapy include suppression of adrenal function, growth, and bone development. Proper interpretation of ICS safety studies requires knowledge of differences between various ICS drug/delivery device systems. Recent findings Dosage, type of inhaler device used, patient technique, and characteristics of the individual drug influence systemic effects of ICS. Reports of adrenal insufficiency occur but are rare and are confined to children receiving high doses of ICS. Dose-related inhibition of growth is detectable as ICS dosage increases, but appears temporary, more pronounced in childhood, and is not associated with reduction in final height. Moderate-dose ICS therapy is not associated with significant changes in measurements of bone density, but more studies of high doses and of therapy in adolescents are needed. Summary Recent studies confirm that benefits of ICS, properly prescribed and used, clearly outweigh not only their potential adverse effects but also the risks associated with poorly controlled asthma.
Radiative RF antenna arrays for cardiac, brain and thermal magnetic resonance at ultrahigh and extreme magnetic field strengths: Concepts, electromagnetic field simulations and applications

A growing number of reports speak about explorations into magnetic resonance (MR) at ultrahigh magnetic fields (UHF-MR, B0≥7.0T). Realizing the research promises and clinical applications of UHF-MR this work outlines current trends in enabling radiofrequency (RF) technology tailored for MR in the low wavelength regime. For this purpose RF technology concepts based upon radiative antennae are discussed. Early applications in cardiac, brain and thermal MR at ultrahigh and extreme magnetic field strengths (B0≥11.7 T) are surveyed. The goal here is not to be comprehensive but to inspire the biomedical engineering, imaging sciences and diagnostic imaging communities to throw further weight behind the solution of the many remaining obstacles of UHF-MR with the goal to transfer MR engineering and MR physics driven methodological advancements into extra clinical value and novel applications.
A Machine Learning-based Framework to Identify Type 2 Diabetes through Electronic Health Records

Objective To discover diverse genotype-phenotype associations affiliated with Type 2 Diabetes Mellitus (T2DM) via genome-wide association study (GWAS) and phenome-wide association study (PheWAS), more cases (T2DM subjects) and controls (subjects without T2DM) are required to be identified (e.g., via Electronic Health Records (EHR)). However, existing expert based identification algorithms often suffer in a low recall rate and could miss a large number of valuable samples under conservative filtering standards. The goal of this work is to develop a semi-automated framework based on machine learning as a pilot study to liberalize filtering criteria to improve recall rate with a keeping of low false positive rate. Materials and Methods We propose a data informed framework for identifying subjects with and without T2DM from EHR via feature engineering and machine learning. We evaluate and contrast the identification performance of widely-used machine learning models within our framework, including k-Nearest-Neighbors, Naïve Bayes, Decision Tree, Random Forest, Support Vector Machine and Logistic Regression. Our framework was conducted on 300 patient samples (161 cases, 60 controls and 79 unconfirmed subjects), randomly selected from 23,281 diabetes related cohort retrieved from a regional distributed EHR repository ranging from 2012 to 2014. Results We apply top-performing machine learning algorithms on the engineered features. We benchmark and contrast the accuracy, precision, AUC, sensitivity and specificity of classification models against the state-of-the-art expert algorithm for identification of T2DM subjects. Our results indicate that the framework achieved high identification performances (~0.98 in average AUC), which are much higher than the state-of-the-art algorithm (0.71 in AUC). Discussion Expert algorithm-based identification of T2DM subjects from EHR is often hampered by the high missing rates due to their conservative selection criteria. Our framework leverages machine learning and feature engineering to loosen such selection criteria to achieve a high identification rate of cases and controls. Conclusions Our proposed framework demonstrates a more accurate and efficient approach for identifying subjects with and without T2DM from EHR.
Differentiated sympathetic neural control of the kidney.

Anatomic and neurophysiological methods were used to identify functionally specific subgroups of renal sympathetic nerve fibers. The distribution of diameters of the predominating unmyelinated fibers showed a major mode at 1.1 microns and a minor mode at 1.6 microns. The conduction velocity was 2.10 +/- 0.10 m/s, consistent with unmyelinated C fibers. Analysis of strength-duration relationships during renal nerve stimulation showed that both rheobase and chronaxie values for renal blood flow were greater than those for urinary flow rate and were independent of stimulation frequency. This difference suggests a higher stimulation threshold (smaller diameter) for those renal nerve fibers involved in the renal blood flow response (renal vasoconstriction) compared with those for the urinary flow rate response (antidiuresis) to renal nerve stimulation. Single renal units that responded to preganglionic splanchnic nerve stimulation were studied. Those with spontaneous activity (88%) responded to stimulation of arterial baroreceptors, arterial and central chemoreceptors, and peripheral thermoreceptors, whereas those that lacked spontaneous activity (12%) responded only to stimulation of peripheral thermoreceptors (known to produce renal vasoconstriction). A minority population of single renal units has been identified that, although renal vasoconstrictor, does not exhibit other characteristic features of vasoconstrictor neurons (i.e., responsiveness to stimulation of arterial baroreceptors and arterial and central chemoreceptors). These findings suggest the existence of functionally specific subgroups of renal nerve fibers.
Factors Hindering the Adoption of Business-to-Consumer (B2C) in Developing Countries: A Case Study of Sudan

It has been commonly reported that e-commerce (electronic commerce) offers viable solutions to businesses in meeting the challenges of an environment that is undergoing changes. This study seeks to explore the factors that influence the adoption decision of Business-to-Consumer (B2C) e-commerce, using Sudan as a case study. The mixed method design was adopted in two stages in which both exploratory and descriptive research approaches were undertaken. Data was collected from enterprises by questionnaire and through the analysis of research and semi-structured interviews. The findings revealed that most enterprises in the country are still in the initial stages of adoption of B2C e-commerce despite the wide growth of Internet use among enterprises in Sudan. Many factors could be responsible for the low usage of e-commerce among the enterprises in Sudan. Technical barrier is seen as the major barrier that affects the adoption of B2C e-commerce. However, this is accompanied by regulatory and legal barriers. One of the factors that inhibit e-commerce adoption in SMEs in Sudan is the lack of Internet security. Other factors include limited use of web portals and Internet banking by enterprises. The use of credit card and visa card is prohibited in Sudan due to the sanction from the United States of America. However, these issues resulted in all type of transactions that involves carrying cash. This makes it risky for customer who carry huge sum of money. In order to improve B2C e-commerce adoption technologies, this study plays a significant role to organizations and supporting organizations, especially those operating in countries with a unique situation like Sudan.
Nitric Oxide Signaling in Brain Function, Dysfunction, and Dementia

Nitric oxide (NO) is an important signaling molecule that is widely used in the nervous system. With recognition of its roles in synaptic plasticity (long-term potentiation, LTP; long-term depression, LTD) and elucidation of calcium-dependent, NMDAR-mediated activation of neuronal nitric oxide synthase (nNOS), numerous molecular and pharmacological tools have been used to explore the physiology and pathological consequences for nitrergic signaling. In this review, the authors summarize the current understanding of this subtle signaling pathway, discuss the evidence for nitrergic modulation of ion channels and homeostatic modulation of intrinsic excitability, and speculate about the pathological consequences of spillover between different nitrergic compartments in contributing to aberrant signaling in neurodegenerative disorders. Accumulating evidence points to various ion channels and particularly voltage-gated potassium channels as signaling targets, whereby NO mediates activity-dependent control of intrinsic neuronal excitability; such changes could underlie broader mechanisms of synaptic plasticity across neuronal networks. In addition, the inability to constrain NO diffusion suggests that spillover from endothelium (eNOS) and/or immune compartments (iNOS) into the nervous system provides potential pathological sources of NO and where control failure in these other systems could have broader neurological implications. Abnormal NO signaling could therefore contribute to a variety of neurodegenerative pathologies such as stroke/excitotoxicity, Alzheimer’s disease, multiple sclerosis, and Parkinson’s disease.
Mandatory Audit Firm Rotation and Prohibition of Audit Firm‐Provided Tax Services: Evidence from Investment Consultants’ Perceptions

The European Union has discussed and recently implemented both audit&#8208;firm instead of audit&#8208;partner rotation and a restriction against audit&#8208;firm&#8208;provided tax services in order to improve auditor independence and audit quality. This study provides experimental evidence of the effects of the rotation system, the impact of audit&#8208;firm&#8208;provided tax services, and, for the first time, the interplay between both regulatory measures. Based on the assessments of 140 professional investment consultants from credit institutions, the results show that an audit&#8208;partner rotation regime which allows audit&#8208;firm&#8208;provided tax services generates the lowest assessments of auditor independence and audit quality. While investment consultants view both audit&#8208;firm rotation and a prohibition against audit&#8208;firm&#8208;provided tax services as beneficial, the joint implementation of a prohibition against audit&#8208;firm&#8208;provided tax services and audit&#8208;firm rotation leads to no additional benefits in either the appearance of independence or the perceived audit quality. Besides the theoretical contribution, we discuss the practical implications of our findings, in particular that more regulation does not automatically lead to higher audit quality.
Staphylococcus aureus ArcR Controls Expression of the Arginine Deiminase Operon

ABSTRACT We identified a single open reading frame that is strongly similar to ArcR, a member of the Crp/Fnr family of bacterial transcriptional regulators, in all sequenced Staphylococcus aureus genomes. The arcR gene encoding ArcR forms an operon with the arginine deiminase (ADI) pathway genes arcABDC that enable the utilization of arginine as a source of energy for growth under anaerobic conditions. In this report, we show that under anaerobic conditions, S. aureus growth is subject to glucose catabolic repression and is enhanced by arginine. Likewise, glucose and arginine have reciprocal effects on the transcription of the arcABDCR genes. Furthermore, we show using a mutant deleted for arcR that the transcription of the arc operon under anaerobic conditions depends strictly on a functional ArcR. These findings are supported by proteome analyses, which showed that under anaerobic conditions the expression of the ADI catabolic proteins depends on ArcR. Bioinformatic analysis of S. aureus ArcR predicts an N-terminal nucleotide binding domain and a C-terminal helix-turn-helix DNA binding motif. ArcR binds to a conserved Crp-like sequence motif, TGTGA-N6-TCACA, present in the arc promoter region and thereby activates the expression of the ADI pathway genes. Crp-like sequence motifs were also found in the regulatory regions of some 30 other S. aureus genes mostly encoding anaerobic enzymatic systems, virulence factors, and regulatory systems. ArcR was tested and found to bind to the regulatory regions of four such genes, adh1, lctE, srrAB, and lukM. In one case, for lctE, encoding l-lactate dehydrogenase, ArcR was able to bind only in the presence of cyclic AMP. These observations suggest that ArcR is likely to play an important role in the expression of numerous genes required for anaerobic growth.
Relationship of In-Hospital Medication Modifications of Elderly Patients to Postdischarge Medications, Adherence, and Mortality

Background: Medication regimens are constantly modified and updated during a patient's hospitalization. These modifications and those made after discharge might increase the risk for nonadherence, polypharmacy, and poor outcomes among elderly patients. Objectives: To investigate the extent of in-hospital modification of medication regimens of elderly patients and its relationship to medication adherence as well as one-month postdischarge drug regimen modifications and to examine the relationship of the modifications, adherence, and polypharmacy to mortality and readmissions 3 months postdischarge. Methods: Clinical and demographic data, postdischarge medication modifications, and adherence were prospectively obtained in 212 elderly patients. Inhospital drug regimen modifications were retrospectively recorded. Results: The average ± SD in-hospital medication regimen modification rate was 49.8% ± 28.4. No modifications were found in 9.7% of the patients. Using demographic and clinical parameters, we performed regression analysis and found that patients who were admitted with polypharmacy, discharged home, and cognitively normal experienced fewer medication modifications (p conclusions: Hospitalization of elderly patients is characterized by extensive medication regimen modifications, which are directly correlated with postdischarge modifications and may indicate an increased risk of mortality.
Age‐related changes in the occurrence and characteristics of thymic CD4+ CD25+ T cells in mice

Natural regulatory CD4+ CD25+ T cells play an important role in preventing autoimmunity by maintaining self‐tolerance. They express CD25 constitutively and are produced in the thymus as a functionally mature T‐cell population. Changes in the potential of these cells to regulate the activity of conventional effector lymphocytes may contribute to an increased susceptibility to infection, cancer and age‐associated autoimmune diseases. In this study we demonstrated that the thymi of aged mice are populated by a higher percentage of CD4+ CD25+ thymocytes than in young animals. The expression of several surface markers (CD69, CD5, CD28, CTLA‐4, CD122, FOXP3), usually used to characterize the phenotype of CD4+ CD25+ T regulatory cells, was compared between young and aged mice. We also examined the ability of sorted thymus‐deriving regulatory T cells of young and aged BALB/c mice to inhibit the proliferation of lymph node lymphocytes activated in vitro. Natural regulatory T cells isolated from the thymi of young mice suppress the proliferation of responder lymph node cells. We demonstrated that thymus‐deriving CD4+ CD25+ T cells of old mice maintain their potential to suppress the proliferation of activated responder lymphocytes of young mice. However, their potential to inhibit the proliferation of old responder T cells is abrogated. Differences in the occurrence and activity of CD4+ CD25+ thymocytes between young and old animals are discussed in relation to the expression of these surface markers.
Fentanyl HCl Patient-Controlled lontophoretic Transdermal System for the Management of Acute Postoperative Pain

Objective: To summarize the pharmaceutics, pharmacokinetics, development, and clinical application of IONSYS, the fentanyl HCl patient-controlled iontophoretic transdermal system for the management of acute postoperative pain. Data Sources: Clinical literature including both primary sources and review articles was accessed through a search of the MEDLINE databases (1980–October 2006). Key search terms included cutaneous analgesia, fentanyl, IONSYS, opioid, postoperative pain, and patient-controlled analgesia (PCA). Additional clinical trial and drug data were supplied by the manufacturer, the ALZA Corporation. Study Selection and Data Extraction: Review articles, abstracts, and clinical studies related to patient-controlled iontophoretic transdermal fentanyl and postoperative pain management were analyzed. An evaluation of the research exploring IONSYS for the management of acute postoperative pain was conducted. Relevant information was then selected and is provided in this article. Data Synthesis: IONSYS is the first iontophoretic transdermal drug delivery system that utilizes low-level electrical energy to actively transport ionized fentanyl HCl through intact skin. Research has revealed that use of IONSYS for patients with acute postoperative pain is safe, effective, and well tolerated. Phase I–III trials have demonstrated an appropriate dosing range leading to effective analgesia, with minimal adverse effects. The analgesia provided by this system was found to be superior to that of analgesia placebo and equivalent to that of an intravenous morphine PCA. Conclusions: Data from clinical trials indicated that IONSYS is successful in controlling acute postoperative pain that circumvents the limitations of intravenous patient-controlled analgesia. The use of this system may serve as an alternative modality for the management of acute pain without increasing such adverse effects as bleeding, intravenous catheter infiltration, or manual pump malfunction.
Inhaled nitric oxide reduces the need for extracorporeal membrane oxygenation in infants with persistent pulmonary hypertension of the newborn

ObjectiveWe previously reported improved oxygenation, but no change, in rates of extracorporeal membrane oxygenation (ECMO) use or death among infants with persistent pulmonary hypertension of the newborn who received inhaled nitric oxide (NO) with conventional ventilation, irrespective of lung disease. The goal of our study was to determine whether treatment with inhaled NO improves oxygenation and clinical outcomes in infants with persistent pulmonary hypertension of the newborn and associated lung disease who are ventilated with high-frequency oscillatory ventilation (HFOV). DesignSingle-center, prospective, randomized, controlled trial. SettingNewborn intensive care unit of a tertiary care teaching hospital. PatientsWe studied infants with a gestational age of ≥34 wks who were receiving mechanical ventilatory support and had echocardiographic and clinical evidence of pulmonary hypertension and hypoxemia (Pao2 ≤100 mm Hg on Fio2 = 1.0), despite optimal medical management. Infants with congenital heart disease, diaphragmatic hernia, or other major anomalies were excluded. InterventionsThe treatment group received inhaled NO, whereas the control group did not. Adjunct therapies and ECMO criteria were the same in the two groups of patients. Investigators and clinicians were not masked as to treatment assignment, and no crossover of patients was permitted. Measurements and Main ResultsPrimary outcome variables were mortality and use of ECMO. Secondary outcomes included change in oxygenation and duration of mechanical ventilatory support and supplemental oxygen therapy. Forty-two patients were enrolled. Baseline oxygenation and clinical characteristics were similar in the two groups of patients. Infants in the inhaled NO group (n = 21) had improved measures of oxygenation at 15 mins and 1 hr after enrollment compared with infants in the control group (n = 20). Fewer infants in the inhaled NO group compared with the control group were treated with ECMO (14% vs. 55%, respectively;p = .007). Mortality did not differ with treatment assignment. ConclusionsAmong infants ventilated by HFOV, those receiving inhaled NO had a reduced need for ECMO. We speculate that HFOV enhances the effectiveness of inhaled NO treatment in infants with persistent pulmonary hypertension of the newborn and associated lung disease.
Accounting For The Situational Context Of Accountability

Accountability is often presented as a panacea for behavioral ailments. This one-size-fits-all approach to a multi-dimensional construct ignores a key component of the effectiveness of accountability systems: situational context. Situational contexts such as highly stochastic environments (e.g., financial markets, world politics) and politically-charged domains (e.g., national security decision-making, domestic policy) form accountability boundary conditions, beyond which previous experimental effects may not generalize. In a series of studies, I explore the relatively under-explored frontiers of accountability effects, including those that apply to highly stochastic environments; politically-charged outcomes, where the tendency towards motivated reasoning dominates; and rapidly evolving states of information, where one’s ability to update one’s beliefs has serious implications for the quality of one’s judgments and decisions. In this series of studies, I find that accountability effects only appeared under certain conditions. In general, holding people accountable for their judgments did not improve performance on highly stochastic or politically-charged tasks—in fact, it sometimes made performance worse. However, certain types of accountability were able to boost performance in some contexts. These studies demonstrate the value of incorporating situational context into accountability experiments. Degree Type Dissertation Degree Name Doctor of Philosophy (PhD) Graduate Group Psychology First Advisor Philip E. Tetlock
Inflammation and Skin Cancer: Old Pals Telling New Stories

Abstract Inflammation and the inflammatory infiltrate essentially contribute to tumor development and progression. For skin cancer, the observation that tumors arise in sites of chronic irritation and inflammation dates back to 1828 and has stimulated a whole field of research. Numerous animal models such as models of UV-induced or chemically induced skin carcinogenesis but also trangenic models support the role of a deregulated inflammation in the development of skin cancer. These models have greatly contributed to our understanding of the multistage process of carcinogenesis and have given important insights in the differences between physiological inflammation in a healing wound and the functional contribution of the deregulated tumor-associated inflammation to skin cancer growth and progression. Data from these models are supported by epidemiological studies that emphasize a connection of inflammatory conditions with the development of melanoma and epithelial skin cancer and give first indications for a beneficial effect of anti-inflammatory treatments in reducing the risk for skin cancer. Consequently, anti-inflammatory drugs might represent a highly interesting approach in the prevention and treatment of skin cancers.