Miracle-dz/UniFAR-FTUs huggingface dataset:
CALL FOR PAPERS Renal Hemodynamics: Integrating with the Nephron and Beyond Role of soluble guanylate cyclase in renal hemodynamics and autoregulation in the rat

Dautzenberg M, Kahnert A, Stasch JP, Just A. Role of soluble guanylate cyclase in renal hemodynamics and autoregulation in the rat. Am J Physiol Renal Physiol 307: F1003–F1012, 2014. First published September 10, 2014; doi:10.1152/ajprenal.00229. 2014. —We studied the influence of soluble guanylate (sGC) on renal blood flow (RBF), glomerular filtration rate (GFR), and RBF autoregulation and its role in mediating the hemodynamic effects of endogenous nitric oxide (NO). Arterial pressure (AP), heart rate (HR), RBF, GFR, urine flow (UV), and the efficiency and mechanisms of RBF autoregulation were studied in anesthetized rats during intravenous infusion of sGC activator cinaciguat before and (except GFR) also after inhibition of NO synthase (NOS) by N -nitro-L-arginine methyl ester. Cinaciguat (0.1, 0.3, 1, 3, 10 g·kg ·min , n 7) reduced AP and increased HR, but did not significantly alter RBF. In clearance experiments (FITC-sinistrin, n 7) GFR was not significantly altered by cinaciguat (0.1 and 1 g·kg ·min ), but RBF slightly rose ( 12%) and filtration fraction (FF) fell ( 23%). RBF autoregulatory efficiency (67 vs. 104%) and myogenic response (33 vs. 44 units) were slightly depressed (n 9). NOS inhibition (n 7) increased AP ( 38 mmHg), reduced RBF ( 53%), and greatly augmented the myogenic response in RBF autoregulation (97 vs. 35 units), attenuating the other regulatory mechanisms. These changes were reversed by 77, 78, and 90% by 1 g·kg ·min 1 cinaciguat. In vehicle controls (n 3), in which cinaciguat-induced hypotension was mimicked by aortic compression, the NOS inhibition-induced changes were not affected. We conclude that sGC activation leaves RBF and GFR well maintained despite hypotension and only slightly impairs autoregulation. The ability to largely normalize AP, RBF, RBF autoregulation, and renovascular myogenic response after NOS inhibition indicates that these hemodynamic effects of NO are predominantly mediated via sGC.
Effect of Lipid Lowering With Rosuvastatin on Progression of Aortic Stenosis: Results of the Aortic Stenosis Progression Observation: Measuring Effects of Rosuvastatin (ASTRONOMER) Trial

Background— Aortic stenosis (AS) is an active process with similarities to atherosclerosis. The objective of this study was to assess the effect of cholesterol lowering with rosuvastatin on the progression of AS. Methods and Results— This was a randomized, double-blind, placebo-controlled trial in asymptomatic patients with mild to moderate AS and no clinical indications for cholesterol lowering. The patients were randomized to receive either placebo or rosuvastatin 40 mg daily. A total of 269 patients were randomized: 134 patients to rosuvastatin 40 mg daily and 135 patients to placebo. Annual echocardiograms were performed to assess AS progression, which was the primary outcome; the median follow-up was 3.5 years. The peak AS gradient increased in patients receiving rosuvastatin from a baseline of 40.8±11.1 to 57.8±22.7 mm Hg at the end of follow-up and in patients with placebo from 41.6±10.9 mm Hg at baseline to 54.8±19.8 mm Hg at the end of follow-up. The annualized increase in the peak AS gradient was 6.3±6.9 mm Hg in the rosuvastatin group and 6.1±8.2 mm Hg in the placebo group (P=0.83). Treatment with rosuvastatin was not associated with a reduction in AS progression in any of the predefined subgroups. Conclusion— Cholesterol lowering with rosuvastatin 40 mg did not reduce the progression of AS in patients with mild to moderate AS; thus, statins should not be used for the sole purpose of reducing the progression of AS. Clinical Trial Registration Information— URL: http://www.controlled-trials.com/. Clinical trial registration number: ISRCTN 32424163.
FL/GCSF/AMD3100-mobilized Hematopoietic Stem Cells Induce Mixed Chimerism With Nonmyeloablative Conditioning and Transplantation Tolerance.

BACKGROUND Mobilization of hematopoietic stem cells (HSCs) has become the preferred approach for HSC transplantation. AMD3100, a competitive inhibitor of C-X-C motif chemokine receptor-4, has been found to be a rapid mobilizing agent. The present study evaluated approaches to optimize the product collected. METHODS Mobilized peripheral blood mononuclear cells (mPBMCs) from B6 mice were transplanted to recipient BALB/c mice conditioned with ablative or nonmyeloablative approaches. RESULTS The optimal dose of AMD3100 was found to be 5.0 mg/kg. Optimal HSC mobilization was observed when AMD3100 (day 10) was coadministered with Flt3 ligand (FL) (days 1-10) and granulocyte colony-stimulating factor (GCSF) (days 4-10). There was a 228.8-fold increase of HSC with FL/GCSF/AMD3100 compared with AMD3100 treatment alone. When unmodified mPBMCs were transplanted into ablated allogeneic recipients, all recipients expired by day 40 from severe acute graft versus host disease (GVHD). When T cells were depleted from mPBMC, long-term survival and engraftment were achieved in majority of the recipients. When PBMC mobilized by FL/GCSF/AMD3100 were transplanted into recipients conditioned nonmyeloablatively with anti-CD154/rapamycin plus 100, 200, and 300 cGy of total body irradiation, 42.9%, 85.7%, and 100% of mice engrafted, respectively. Donor chimerism was durable, multilineage, and stable. Lymphocytes from mixed chimeras showed no response to host or donor antigens, suggesting functional bidirection T-cell tolerance in vitro. Most importantly, none of the engrafted mice exhibited clinical features of GVHD. CONCLUSIONS FL/GCSF/AMD3100 is an efficient treatment to maximally mobilize HSC. Durable engraftment and donor-specific tolerance can be achieved with mPBMC in nonmyeloablative conditioning without GVHD.
Purification and characteristics of an aflatoxin B1 degradation enzyme isolated from Pseudomonas aeruginosa.

Aflatoxin is a highly toxic mycotoxin produced by Aspergillus flavus and Aspergillusparasiticus fungus. Since it contaminates food and grain widely, it has seriously endanger the health of human beings and animals. Some microorganisms that exist in nature can degrade aflatoxin. In this paper, the biological AFB1 (aflatoxin B1)-degradation by Pseudomonas aeruginosa M19 was evaluated. We found that the culture supernatant of P. aeruginosa M19 added with proteinase K (Prok), SDS and heating significantly decreased degradation capacity. Pseudomonas AFB1-degrading enzyme (PADE) was purified from P. aeruginosa M19 by a three-step procedure including ammonium sulfate fractional precipitation and ion exchange chromatography and gel filtration chromatography. PADE was purified 175-fold with a recovery of 35%, and an ultimate specific activity of 6.1 × 104 U/mg was achieved. The molecular weight of PADE estimated by SDS-PAGE is about 48 kDa. PADE displayed the highest degradation activity for AFB1 at 65°C and pH 6.0. Cu2+ and Fe3+ strongly enhanced the activity, whereas Ca2+ and Zn2+ strongly inhibited the activity. These findings indicate that PADE from P. aeruginosa M19 is a promising candidate for AFB1 biodegradation.
Evaluation of segmentation algorithms for optical coherence tomography images of ovarian tissue

Abstract. Ovarian cancer has the lowest survival rate among all gynecologic cancers predominantly due to late diagnosis. Early detection of ovarian cancer can increase 5-year survival rates from 40% up to 92%, yet no reliable early detection techniques exist. Optical coherence tomography (OCT) is an emerging technique that provides depth-resolved, high-resolution images of biological tissue in real-time and demonstrates great potential for imaging of ovarian tissue. Mouse models are crucial to quantitatively assess the diagnostic potential of OCT for ovarian cancer imaging; however, due to small organ size, the ovaries must first be separated from the image background using the process of segmentation. Manual segmentation is time-intensive, as OCT yields three-dimensional data. Furthermore, speckle noise complicates OCT images, frustrating many processing techniques. While much work has investigated noise-reduction and automated segmentation for retinal OCT imaging, little has considered the application to the ovaries, which exhibit higher variance and inhomogeneity than the retina. To address these challenges, we evaluate a set of algorithms to segment OCT images of mouse ovaries. We examine five preprocessing techniques and seven segmentation algorithms. While all preprocessing methods improve segmentation, Gaussian filtering is most effective, showing an improvement of 32 % ± 1.2 % . Of the segmentation algorithms, active contours performs best, segmenting with an accuracy of 94.8 % ± 1.2 % compared with manual segmentation. Even so, further optimization could lead to maximizing the performance for segmenting OCT images of the ovaries.
Local frustration around enzyme active sites

Significance All known terrestrial protein enzymes fold robustly and explore the complex energy landscapes that are required for activity. The catalytic residues must be held together in precise positions that may conflict with the correct folding dynamics of the domain itself. We quantified these energetic conflicts and found that these are effectively present in extant enzymes, regardless of the protein oligomeric state, overall topology, and enzymatic class. The conservation of these energetic signatures is higher than the conservation quantified in the primary structures. Conflicting biological goals often meet in the specification of protein sequences for structure and function. Overall, strong energetic conflicts are minimized in folded native states according to the principle of minimal frustration, so that a sequence can spontaneously fold, but local violations of this principle open up the possibility to encode the complex energy landscapes that are required for active biological functions. We survey the local energetic frustration patterns of all protein enzymes with known structures and experimentally annotated catalytic residues. In agreement with previous hypotheses, the catalytic sites themselves are often highly frustrated regardless of the protein oligomeric state, overall topology, and enzymatic class. At the same time a secondary shell of more weakly frustrated interactions surrounds the catalytic site itself. We evaluate the conservation of these energetic signatures in various family members of major enzyme classes, showing that local frustration is evolutionarily more conserved than the primary structure itself.
Artificial Neural Network for in-Bed Posture Classification Using Bed-Sheet Pressure Sensors

Pressure ulcer prevention is a vital procedure for patients undergoing long-term hospitalization. A human body lying posture (HBLP) monitoring system is essential to reschedule posture change for patients. Video surveillance, the conventional method of HBLP monitoring, suffers from various limitations, such as subject's privacy, and field-of-view obstruction. We propose an autonomous method for classifying the four state-of-the-art HBLPs in healthy adults subjects: supine, prone, left and right lateral, with no sensors or cables attached on the body and no constraints imposed on the subject. Experiments have been conducted on 12 healthy adults (age 27.35 $\pm$ 5.39 years) using a collection of textile pressure sensors embedded in a cover placed under the bed sheet. Histogram of oriented gradients and local binary patterns were extracted and fed to a supervised artificial neural network classification model. The model was trained based on the scaled conjugate gradient backpropagation. A nested cross validation with an exhaustive outer validation loop was performed to validate the classification's generalization performance. A high testing prediction accuracy of 97.9% with a Cohen's Kappa coefficient of 97.2% has been interestingly obtained. Prone and supine postures were successfully separated in the classification, in contrast to the majority of previous similar works. We found that using the information of body weight distribution along with the shape and edges contributes to a better classification performance and the ability to separate supine and prone postures. The results are satisfactorily promising toward unobtrusively monitoring posture for ulcer prevention. The method can be used in sleep studies, post-surgical procedures, or applications requiring HBLP identification.
Radiofrequency phase encoded half‐pulses in simultaneous multislice ultrashort echo time imaging

To describe a simultaneous multislice (SMS) ultrashort echo time (UTE) imaging method using radiofrequency phase encoded half‐pulses in combination with power independent of number of slices (PINS) inversion recovery (IR) pulses to generate multiple‐slice images with short T2* contrasts in less than 3 min with close to an eightfold acceleration compared with a standard 2D approach.
Uveitis Subtypes in a German Interdisciplinary Uveitis Center—Analysis of 1916 Patients

Objective Studies on the epidemiology of uveitis are rare and cohorts are small. We analyzed the frequencies of classified forms of uveitis in all patients at our center. Methods We studied 1916 consecutive patients with inflammatory eye disease. Data were analyzed regarding associated systemic disease, infection, ocular syndromes, anatomic localization, age, and sex. Results In 59.1% of patients, a classified form of uveitis was observed: associated systemic diseases in 43.7%, the most frequent ones sarcoidosis (17.4%) and ankylosing spondylitis (16.8%); ocular syndromes in 34.3%, the most frequent HLA-B27-positive anterior uveitis (AU; 35.1%) and Fuchs uveitis syndrome (FUS; 34.3%); and infections in 22.4%, the most frequent herpetic infections (46.1%) and toxoplasmosis (31.5%). We found AU in 45.4% of patients (15.4% HLA-B27-positive AU and 11.3% FUS), intermediate uveitis in 22.9% (unclassified 53.7% and multiple sclerosis 10.3%), and posterior uveitis in 13.5% (24.7% toxoplasmosis). Panuveitis was diagnosed in 6.2% of cases (Behçet’s disease 12.6%; sarcoidosis 10.9%). The remaining 12.0% of cases showed extrauveal manifestations (scleritis, episcleritis, keratitis, optic neuritis, myositis, and orbital inflammation). Conclusion We describe the largest cohort to date of consecutive patients from a specialized uveitis center. The high frequency of classified disease, nearly 60% in our clinic, shows the usefulness of an interdisciplinary approach, oriented on anatomic presentation.
Age-related differences in water and sodium handling after commercial hydration beverage ingestion.

Aging is associated with altered water, electrolyte, and glucose handling. Alternative beverages to those containing carbohydrate (CHO) should be considered for older adults. We hypothesized that reduced sodium (CNa+) and/or water (CH2O) clearance would underlie greater beverage retention in older compared with young adults, secondary to reduced glomerular filtration rate (GFR). We further hypothesized that amino acid (AA)- and CHO-based beverages would promote retention better than water. Over five visits, 12 young (23 ± 3 yr; 7 men, 5 women) and 12 older (67 ± 6 yr; 5 men, 7 women) subjects consumed 1 liter of distilled water or beverages with 6% CHO, 0.46 g/l Na+ [Gatorade (GAT)]; 2.5% CHO, 0.74 g/l Na+ [Pedialyte (PED)]; 5 AA, 1.04 g/l Na+ [enterade (ENT)-5]; or 8 AA, 1.38 g/l Na+ (ENT-8) over 30 min. Blood and urine were collected every hour for 4 h after ingestion; retention, CH2O, and CNa+ were calculated at 2 and 4 h. Additional calculations adjusted CH2O and CNa+ for estimated GFR (eGFR). Water yielded the lowest retention in both groups ( P ≤ 0.02). Retention was higher in older vs. young adults except for ENT-8 at 4 h ( P = 0.73). CH2O was higher for older vs. young adults for GAT at 2 h ( P < 0.01) and GAT and PED at 4 h ( P < 0.01) after ingestion but was otherwise similar between groups. CNa+ was lower in older vs. young adults except for ENT-8 ( P ≥ 0.19). Adjusting for eGFR resulted in higher CH2O for all beverages in older vs. young adults ( P < 0.05) but did not influence CNa+. Older adults may better retain beverages with less Na+ than young adults because of reduced CNa+. AA- and CHO-based electrolyte-rich beverages may similarly promote beverage retention. NEW & NOTEWORTHY Commercially available amino acid (AA)-containing beverages may provide an alternative to traditional carbohydrate (CHO)-containing beverages, particularly for older adults with attenuated water, electrolyte, and glucose handling. We compared beverage retention and free water and sodium clearance between young and older adults after ingestion of water, two CHO-based beverages, and two AA-based beverages. Our data suggest that older adults better retain beverages with less sodium compared with young adults and that AA-based and CHO-based electrolyte-containing beverages similarly promote retention.
Molecular control of protein synthesis, glucose metabolism, and apoptosis in the brain of hibernating thirteen-lined ground squirrels.

Thirteen-lined ground squirrels (Ictidomys tridecemlineatus) are excellent models for studying acute brain ischemia since they show high resistance to reductions in blood flow and oxygen delivery without evidence of neurological damage. In the present study, we analyzed the insulin signaling pathway and regulation of mitochondrial substrate oxidation in three regions of ground squirrel brain (forebrain, cerebellum, and brainstem), comparing summer, late torpor, and interbout arousal conditions. We found select decreases in phospho-Akt in the cerebellum during torpor as compared to summer animals, as well as select increases in the forebrain during interbout arousal, suggesting that Akt may influence either metabolism or cytoprotective pathways. The phosphoprotein abundance of GSK3β showed the most consistent trend across all three brain regions with peak increases observed during deep torpor, suggesting a crucial role for this protein during hibernation. Furthermore, all three regions of the brain showed increased phospho-protein abundance of pyruvate dehydrogenase at serine 232 during both deep torpor and interbout arousal and serine 300 during interbout arousal only, whereas phosphorylation sites showed a region-specific expression pattern. Information collected from these studies sheds light on the molecular controls governing insulin signaling and fuel utilization in the brain of hibernating ground squirrels.
Configuration of the circle of Willis and its two parts among Egyptian: a magnetic resonance angiographic study.

BACKGROUND We hypothesized that the collateral circulation differs in different ethnic groups. So, the aim of our work was to study variations of the circle of Willis (COW) among Egyptian and to compare our findings with the findings of other nationalities. MATERIAL AND METHODS One hundred patients were studied using magnetic resonance angiographic (3D-TOF-MRA). Frequency and morphologic variations in COW were studied. The diameters of the arteries of the anterior and posterior circle were verified. Finally, the differences among the mean diameters of these arteries regarding age and sex were also studied. RESULTS Complete, partially complete and incomplete COW were encountered in 28%, 38% and 34% in the studied cases. The incomplete anterior circle was found in 34% (10 % isolated incomplete anterior circle and 24% combined incomplete anterior and posterior circles) and the incomplete posterior circle came across in 62% (38% isolated incomplete posterior circle and 24% combined incomplete anterior and posterior circles). Seven anterior circle variations were found. The commonest type was the classical type "a" with a prevalence of 56%, being higher in male (57.1%). The 2nd common type was type "g" (hypoplasia or aplasia of the anterior communicating artery) with a prevalence of 24 %, being higher in male (66.7%). Six posterior circle variations were found. The commonest variation was the classic type "a" with a prevalence of 26%, being higher in male (61.5%). Posterior circles types "d, e, h" (18%, 24%, 20%) constituted 62% and were characterized by hypoplasia/absent of the posterior communicating arteries. CONCLUSIONS The prevalence of complete COW (classic or textbook type) was encountered only 28% of the studied cases. Variations of COW were found to be more common in the posterior circulation (62%). The incomplete anterior circle was found in 34% and it is mostly caused by hypoplasia or aplasia of the anterior communicating artery which was found to be more common compared to the literature.
Pharmacokinetics, Safety, and Tolerability of Oxfendazole in Healthy Volunteers: a Randomized, Placebo-Controlled First-in-Human Single-Dose Escalation Study

Cysticercosis is a parasitic disease that frequently involves the human central nervous system (CNS), and current treatment options are limited. Oxfendazole, a veterinary medicine belonging to the benzimidazole family of anthelmintic drugs, has demonstrated substantial activity against the tissue stages of Taenia solium and has potential to be developed as an effective therapy for neurocysticercosis. ABSTRACT Cysticercosis is a parasitic disease that frequently involves the human central nervous system (CNS), and current treatment options are limited. Oxfendazole, a veterinary medicine belonging to the benzimidazole family of anthelmintic drugs, has demonstrated substantial activity against the tissue stages of Taenia solium and has potential to be developed as an effective therapy for neurocysticercosis. To accelerate the transition of oxfendazole from veterinary to human use, the pharmacokinetics, safety, and tolerability of oxfendazole were evaluated in healthy volunteers in this phase 1 first-in-human (FIH) study. Seventy subjects were randomly assigned to receive a single oral dose of oxfendazole (0.5, 1, 3, 7.5, 15, 30, or 60 mg oxfendazole/kg body weight) or placebo and were followed for 14 days. Blood and urine samples were collected, and the concentrations of oxfendazole were measured using a validated ultraperformance liquid chromatography mass spectrometry method. The pharmacokinetic parameters of oxfendazole were estimated using noncompartmental analysis. Oxfendazole was rapidly absorbed with a mean plasma half-life ranging from 8.5 to 11 h. The renal excretion of oxfendazole was minimal. Oxfendazole exhibited significant nonlinear pharmacokinetics with less than dose-proportional increases in exposure after single oral doses of 0.5 mg/kg to 60 mg/kg. This nonlinearity of oxfendazole is likely due to the dose-dependent decrease in bioavailability that is caused by its low solubility. Oxfendazole was found to be well tolerated in this study at different escalating doses without any serious adverse events (AEs) or deaths. There were no significant differences in the distributions of hematology, biochemistry, or urine parameters between oxfendazole and placebo recipients. (This study has been registered at ClinicalTrials.gov under identifier NCT02234570.)
Mitotic chromosome alignment ensures mitotic fidelity by promoting interchromosomal compaction during anaphase

Chromosome alignment at the equator of the mitotic spindle is a highly conserved step during cell division; however, its importance to genomic stability and cellular fitness is not understood. Normal mammalian somatic cells lacking KIF18A function complete cell division without aligning chromosomes. These alignment-deficient cells display normal chromosome copy numbers in vitro and in vivo, suggesting that chromosome alignment is largely dispensable for maintenance of euploidy. However, we find that loss of chromosome alignment leads to interchromosomal compaction defects during anaphase, abnormal organization of chromosomes into a single nucleus at mitotic exit, and the formation of micronuclei in vitro and in vivo. These defects slow cell proliferation and are associated with impaired postnatal growth and survival in mice. Our studies support a model in which the alignment of mitotic chromosomes promotes proper organization of chromosomes into a single nucleus and continued proliferation by ensuring that chromosomes segregate as a compact mass during anaphase.