Miracle-dz/UniFAR-FTUs huggingface dataset:
Effects of obesity on estradiol metabolism: decreased formation of nonuterotropic metabolites.

Obesity is associated with an increased incidence of reproductive dysfunction and estrogen-linked diseases. In the present study, we have examined the principal oxidative biotransformations of estradiol in 13 obese premenopausal females and 10 obese males compared to those in 9 premenopausal female and 15 male controls. These studies were carried out using a recently devised, sensitive radiometric method which permits the assessment of the total in vivo oxidative metabolism of estradiol at specific sites (i.e. 17 alpha, 16 alpha, or C-2) on the steroid molecule. Our results indicate that obesity (greater than 60% above ideal body weight) is associated with significant decreases in hydroxylation at C-2 in both sexes (P less than 0.001 for females and P less than 0.02 for males) and in oxidation at 17 alpha in premenopausal females (P less than 0.05) compared to that in age-matched, normal weight controls. Analysis of the plasma 3H2O specific activity curves suggested a slight decrease in the rate of 17-oxidation in obese subjects. The extent of hydroxylation at 16 alpha was not significantly affected by obesity. These metabolic alterations documented in obesity could result in a relative hyperestrogenic state, since, unlike the other estrogen metabolites, the 2-hydroxyestrogen compounds display relatively little peripheral estrogenic activity. This metabolic alteration on a prolonged basis might be contributory to the prevalence of certain hormonally related diseases in obese individuals.
The resting‐state neurovascular coupling relationship: rapid changes in spontaneous neural activity in the somatosensory cortex are associated with haemodynamic fluctuations that resemble stimulus‐evoked haemodynamics

Although promise exists for patterns of resting‐state blood oxygen level‐dependent (BOLD) functional magnetic resonance imaging (fMRI) brain connectivity to be used as biomarkers of early brain pathology, a full understanding of the nature of the relationship between neural activity and spontaneous fMRI BOLD fluctuations is required before such data can be correctly interpreted. To investigate this issue, we combined electrophysiological recordings of rapid changes in multi‐laminar local field potentials from the somatosensory cortex of anaesthetized rats with concurrent two‐dimensional optical imaging spectroscopy measurements of resting‐state haemodynamics that underlie fluctuations in the BOLD fMRI signal. After neural ‘events’ were identified, their time points served to indicate the start of an epoch in the accompanying haemodynamic fluctuations. Multiple epochs for both neural ‘events’ and the accompanying haemodynamic fluctuations were averaged. We found that the averaged epochs of resting‐state haemodynamic fluctuations taken after neural ‘events’ closely resembled the temporal profile of stimulus‐evoked cortical haemodynamics. Furthermore, we were able to demonstrate that averaged epochs of resting‐state haemodynamic fluctuations resembling the temporal profile of stimulus‐evoked haemodynamics could also be found after peaks in neural activity filtered into specific electroencephalographic frequency bands (theta, alpha, beta, and gamma). This technique allows investigation of resting‐state neurovascular coupling using methodologies that are directly comparable to that developed for investigating stimulus‐evoked neurovascular responses.
A review of the management of antidepressant discontinuation symptoms

Strong evidence supports the existence of a discontinuation syndrome following the withdrawal of antidepressant medication, particularly second-generation antidepressants. The syndrome is a common phenomenon and guidance as to best avoid the symptoms is essential for both practitioners and patients. The current study reviewed the available literature on the best methods of discontinuation for antidepressants in order to avoid or prevent the occurrence of any unpleasant side effects associated with antidepressant withdrawal. Accordingly, an electronic search of the PubMed/MedLine database and Google Scholar was conducted to find relevant literature published within the last 10 years. From this, 18 related articles were identified; five clinical studies, one case series, one consensus panel’s recommendations and 11 literature reviews. Of the articles reviewed there is a general consensus as to tapering the drug slowly over a period of weeks or months. Also, in those patients who experience severe symptoms the drug should be reinstated and discontinued more gradually. The discontinuation syndrome does not occur as frequently or severely with longer-acting agents such as fluoxetine and therefore it is recommended that switching to this drug prior to withdrawal may be advisable. The articles reviewed also emphasize the need for patient education and reassurance throughout the discontinuation process. One in particular adds that cognitive behavioural therapy may be a useful tool in easing the patients’ distress. However, this review highlights the lack of controlled data to support the available guidelines. Furthermore, the guidance which is available is somewhat conflicting. Research approaches should address this issue as well as develop appropriate methods of withdrawal for specific drugs.
Nano-TiO2 – feasibility and challenges for human health risk assessment based on open literature

Abstract This study aims at investigating feasibility and challenges associated with conducting a human health risk assessment for nano-titanium-dioxide (nano-TiO2) based on the open literature by following an approach similar to a classical regulatory risk assessment. Gaps in the available data set, both in relation to exposures and hazard, do not allow reaching any definite conclusions that could be used for regulatory decision-making. Results show that repeated inhalation in the workplace and possibly consumer inhalation may cause risks. Also short-term inhalation following spray applications may cause risks. Main future work should focus on generating occupational and consumer inhalation exposure data, as well as toxicity data on absorption following inhalation, repeated dermal contact, and contact with damaged skin. Also relevant seems further information on possible neurotoxicity and genotoxicity/carcinogenicity, as well as establishing a No Observed Adverse Effect Level (NOAEL) for acute inhalation of nano-TiO2.
Percutaneous Pedicle Screw Fixation for Neurologic Intact Thoracolumbar Burst Fractures

Study Design Prospective consecutive series. Objective To evaluate the efficacy and safety of percutaneous pedicle screw fixation (PPSF) for thoracolumbar AO type A3 fractures with a specially designed surgical instrument system. Summary of Background Data Minimally invasive surgery including PPSF is becoming increasingly widespread in the spine surgery. The technique of PPSF was mostly used as supplemental fixation combined with minimally invasive posterior or anterior lumbar interbody fusion in management of lumbar degenerative disorders. There are fewer studies available in literature regarding PPSF without additional kyphoplasty or vertebroplasty for management of thoracolumbar burst fractures. Methods Thirty-six adult patients, who had single thoracolumbar AO type A3 fractures and the load-sharing score of 6 or less, underwent application of percutaneous short-segment pedicle screw fixation. Radiologic parameters including kyphotic angle and vertebral height loss were assessed before and after surgery, and functional outcome was evaluated by Prolo questionnaire. Results All patients were successfully managed with percutaneous minimal invasive procedures. The average operative time was 78 minutes (range 62 to 117 min). The average intraoperative blood loss was 75 mL (range 50 to 220 mL). After a mean follow-up of 48.5 months (range 32 to 63 mo), 31 of 36 (86.1%) patients had a satisfactory result (19 excellent and 12 good) and 5 of them fair. Conclusions Our clinical results suggest that PPSF can be an alternative for management of thoracolumbar AO type A3 fractures that have no neurologic deficits. With a specially designed percutaneous instrument and pedicle screw system, the procedure has been proved as relatively safe and a minimally invasive approach for the management of thoracolumbar burst fracture without neurologic deficit.
Counseling Services for Battered Women

Approximately 15% of married or cohabiting women and as many as 60% of battered women are raped at least once by their partners. This study compared community-based counseling outcomes of battered women with outcomes of women who were both raped and battered by their partners. Over time, both groups improved in wellbeing and coping. Although those both battered and raped progressed more in counseling, they had lower scores before and after counseling compared to women who were battered only. Implications for research and intervention are discussed.
Treatment Considerations for Unique Patient Populations With HCV Genotype 1 Infection

Objective: To review the literature for the treatment of hepatitis C virus (HCV) genotype 1 in certain populations of patients that require further considerations before therapy initiation. Data Sources: A systematic electronic literature search using the MEDLINE database was performed using the search terms hepatitis C, chronic hepatitis C, drug therapy, end stage liver disease, liver transplantation, HIV, hepatitis B, African Americans, renal insufficiency, obesity, pregnancy, and pediatrics. Study Selection and Data Extraction: English language studies from January 1985 to March 2015 were considered. Additional references were identified from ongoing trials obtained from clinicaltrials.gov, conference proceedings, online databases, and citations in relevant review articles. Data Selection: Direct-acting antivirals are first-line recommendations for the treatment of HCV genotype 1 infection, and these include combinations of sofosbuvir, simeprevir, ledipasvir/sofosbuvir, ombitasvir/paritaprevir/ritonavir plus dasabuvir, and ribarvirin. Historical and clinical data focusing on the treatment of HCV with these agents in the following populations were selected: decompensated cirrhosis, post-liver transplant, HIV, African Americans, obesity, hepatitis B coinfection, renal impairment, pregnancy, and pediatrics. Conclusion: Depending on the population studied, clinicians must consider differences in efficacy outcomes, potential drug interactions, and adverse effects that patients may experience.
The Experience of Miscarriage in First Pregnancy: The Women's Voices

The study is a qualitative analysis of 19 interviews with Israeli women who have lost a first pregnancy to miscarriage. Neither the public nor health care professionals are fully aware of the implications and significance of miscarriage to the woman who has lost the pregnancy. The goal of this study was to understand and give voice to the women's experience. Five themes were revealed—the greater the joy, the more painful the crash; the nature and intensity of the loss; sources of support; life after the miscarriage; and recommendations to professionals. The experience of miscarriage was found to be grounded in the meaning of being a woman, as the loss of the pregnancy undermines the women's basic belief in their fertility and as a result threatens their meaning and role as women.
Does credit information sharing affect funding cost of banks? Evidence from African banks

This study takes advantage of the lack of empirical studies on the effect of credit information sharing and funding cost of banks and investigates credit information sharing and bank funding cost in Africa between 2006 and 2012. Employing a twoâ€ step generalized method of moments regression of 233 banks in 17 African countries, the study provides new revelations. The study shows that the quality of credit information shared is key and persistent in reducing funding cost of banks. Again, the study confirms that the coverage of private credit bureaus significantly reduced bank funding cost whereas no such evidence was found for coverage of public credit registries. Further, although the study found evidence to support that the presence of credit information reduces bank funding cost, no evidence was found to support that countries that use both private credit bureaus and public credit registries are able to reduce funding cost of banks in Africa. From these results, it is evident that credit information sharing presence, coverage, and quality reduces funding cost in Africa. For policy recommendations, policymakers and bank boards must team up and set up credit information sharing institutions to help reduce information asymmetry and funding cost in countries that do not share credit information. Also, the introduction and establishment of credit information sharing must be geared towards private bureaus as they are more effective in reducing funding cost of banks. Again, policymakers must enact laws and policies that deepen the coverage, depth, and quality of credit information shared so that the financial sector of Africa countries can realize the full potential of credit information sharing.
Low-power microcontroller for wireless sensor networks

The energy constraint in wireless sensor networks (WSNs) advocates the design and use of low power components in sensor nodes. Commercial general purpose microcontrollers are not suitable for such applications and have motivated us towards the design of a low-power microcontroller tailored for the WSN application domain. In this paper, we study the characteristics of typical WSN applications and present the design of a power-aware microcontroller using conventional design techniques. Our simulation results show significant power savings compared to other off-the-shelf microcontrollers.
A nationwide analysis of risk factors for mortality and time to endoscopy in upper gastrointestinal haemorrhage

We analysed nationwide in‐patient data from 2002 to 2007 to determine significant demographic variables when predicting mortality and receipt of prompt oesophagogastroduodenoscopy (OGD) for acute variceal haemorrhage (AVH) and nonvariceal upper gastrointestinal haemorrhage (NVUGIH).
Analysis of LED wire bonding process using arbitrary Lagrangian-Eulerian and explicit time integration methods

Wire bonding is one of the main processes used to connect the signal of light emitting diode (LED) chips. Failures, such as pad peeling, cracking, and delamination, affect the development of LED, and some of these failures are influenced by the wire bonding process. This research aims to construct an effective simulation methodology for the impact stage of the wire bonding process. An effective simulation methodology utilizing the explicit method with a second level accuracy arbitrary Lagrangian-Eulerian (ALE) algorithm is successfully achieved. Only a 0.5% discrepancy in ball height between this model and the actual wire bonding sample is observed after the impact stage, and the geometry of the bonded wire is similar to that of the actual wire. The finite element (FE) model established in this research not only conquers the element distortion problem, but proposes an effective methodology for simulating the wire bonding process in the future.
Comprehensive Proteomics Analysis Reveals New Substrates and Regulators of the Fission Yeast Clp1/Cdc14 Phosphatase*

The conserved family of Cdc14 phosphatases targets cyclin-dependent kinase substrates in yeast, mediating late mitotic signaling events. To discover substrates and regulators of the Schizosaccharomyces pombe Cdc14 phosphatase Clp1, TAP-tagged Clp1, and a substrate trapping mutant (Clp1-C286S) were purified from asynchronous and mitotic (prometaphase and anaphase) cells and binding partners were identified by 2D-LC-MS/MS. Over 100 Clp1-interacting proteins were consistently identified, over 70 of these were enriched in Clp1-C286S-TAP (potential substrates) and we and others detected Cdk1 phosphorylation sites in over half (44/73) of these potential substrates. According to GO annotations, Clp1-interacting proteins are involved in many essential cellular processes including mitosis, cytokinesis, ribosome biogenesis, transcription, and trafficking among others. We confirmed association and dephosphorylation of multiple candidate substrates, including a key scaffolding component of the septation initiation network called Cdc11, an essential kinase of the conserved morphogenesis-related NDR kinase network named Shk1, and multiple Mlu1-binding factor transcriptional regulators. In addition, we identified Sal3, a nuclear β-importin, as the sole karyopherin required for Clp1 nucleoplasmic shuttling, a key mode of Cdc14 phosphatase regulation. Finally, a handful of proteins were more abundant in wild type Clp1-TAP versus Clp1-C286S-TAP, suggesting that they may directly regulate Clp1 signaling or serve as scaffolding platforms to localize Clp1 activity.
Soil development in phosphate-mined created wetlands of Florida, USA

Soil characteristics of a wide variety of created wetlands were compared to those of native wetlands in phosphate-mined areas from central and north Florida, USA. Criteria selected for evaluation of soil samples from 184 sites included soil compaction, bulk density, organic matter (carbon) and nitrogen content, C∶N ratio, and available and total nutrient contents. Organic matter accumulation, one of the indicators of a functional wetland, increased across transects going from uplands toward the center of the wetlands, and with wetland age. The organic matter accumulation rate in the AO and A1 horizons was 320 g m2yr−1. Native wetlands had significantly greater organic matter accumulation, both in the litter and mineral soil surface. The C∶N ratio of the soil organic matter decreased with created wetland age and approached values commonly found in wetland soils (15–25). Bulk density decreased with increasing organic matter content in the created wetlands, and low bulk density soils appeared to support better vegetative growth. Based on the above-mentioned parameters, reclaimed wetlands are slowly developing into “typical” wetlands; the rate of development could possibly be increased by minimizing soil compaction, incorporation of organic matter, or by fertilization.
Levodopa-Induced Dyskinesias in Parkinson Disease Are Independent of the Extent of Striatal Dopaminergic Denervation: A Pharmacological and SPECT Study

The physiopathology of levodopa-induced dyskinesias (LIDs) is unclear. Presynaptic pharmacokinetic and postsynaptic pharmacodynamic mechanisms may be involved. We have analyzed several clinical and pharmacological parameters, as well as the status of the presynaptic dopamine nigrostriatal pathway by using DaTSCAN, in 14 patients with Parkinson disease who developed early and severe LID despite using low doses of levodopa and 10 patients without this complication despite the use of high levodopa doses. Patients were matched for age at onset, duration, and severity of Parkinson disease. Statistically significant differences were observed only in the duration of LID during the levodopa challenge. However, clear differences were also observed in weight and sex distribution (women with low weight predominate in the group with dyskinesia), severity and duration of LID, and total levodopa dosage. The pattern of response to levodopa and the uptake of (123I)N-w-fluoropropyl-2&bgr;-carbomethoxy-3&bgr;-(4-iodophenyl)nortropane were similar in both groups. These results indicate that the development of LID needs additional contributions beyond nigrostriatal denervation. Factors related to sex and body weight could play an important role. However, these findings should be considered cautiously because of the limited statistical power of the study.
Phosphorylation of the serine 60 residue within the Cdx2 activation domain mediates its transactivation capacity.

BACKGROUND & AIMS Cdx2 is critical in intestinal proliferation and differentiation. Modulation of Cdx2 function in response to cellular signaling is to be elucidated. We hypothesize that phosphorylation of the Cdx2 activation domain can modulate its function. METHODS The Cdx2 activation domain was delineated in transient transfections using different portions of Cdx2 fused to the Gal4-DNA binding domain. In vivo phosphorylation was studied by metabolic labeling with (32)P-orthophosphate. To study a potential phosphorylation site, polyclonal antibodies were generated: CNL was raised against amino acids 54-66 of Cdx2 and P-Cdx2-S60 against the same epitope in which serine 60 was phosphorylated. RESULTS A critical region for transactivation resides within amino acids 60-70. Substitution of serine 60 with alanine reduces incorporation of (32)P-orthophosphate substantially. S60-phosphorylation decreases Cdx2 transactivation. Phosphorylation of serine 60 can be inhibited with the mitogen-activated protein kinase inhibitors PD98059 or UO126. P-Cdx2-S60 recognizes phosphorylated serine 60 mainly in proliferative compartment of the intestinal epithelial layer. In contrast, CNL recognizes Cdx2 predominantly in the differentiated compartment. CONCLUSIONS The Cdx2 activation domain is phosphorylated at serine 60 via the mitogen-activated protein kinase pathway. S60-phosphorylated and S60-nonphosphorylated Cdx2 have different transcriptional activity, as well as different spatial expression patterns in the intestinal epithelium.
Exhaled nitric oxide in asthma: progress since the introduction of standardized methodology

The measurement of nitric oxide (NO) in exhaled breath has given us the ability to learn about and monitor the inflammatory status of the airway through a non-invasive method that is easy to perform and repeat. This has been most useful in the diagnosis and management of asthma and has promised a seemingly unlimited potential for evaluating the airways and how clinical decisions are made (Grob N M and Dweik R A 2008 Chest 133 837–9). The exhaled NO field was initially limited, however, due to the absence of standardized methodology. The ATS and ERS jointly released recommendations for standardized methods of measuring and reporting exhaled NO in 1999 that were revised in 2005 (1999 Am. J. Respir. Crit. Care. Med. 160 2104–17; 2005 Am. J. Respir. Crit. Care. Med. 171 912–30). In this paper, we summarize the literature that followed this standardization. We searched the literature for all papers that included the term ‘exhaled nitric oxide’ and selected those that followed ATS guidelines for online measurement for further review. We also reviewed cut-off values suggested by groups studying exhaled nitric oxide. We found a wide range of NO values reported for normal and asthma populations. The geometric mean for FENO ranged from 10 ppb to 33 ppb in healthy adult control populations. For asthma, the FENO geometric mean ranged from 6 ppb to 98 ppb. This considerable variation likely reflects the different clinical settings and purposes of measurement. Exhaled NO has been used for a multitude of reasons that range from screening, to diagnosis, to monitoring the effect of therapy. The field of exhaled NO has made undeniable progress since the standardization of the measurement methods. Our challenge now is to have guidelines to interpret exhaled NO levels in the appropriate context. As the utility of exhaled NO continues to evolve, it can serve as a good example of the crucial role of the standardization of collection and measurement methods to propel any new test in the right direction as it makes its way from a research tool to a clinically useful test.