Miracle-dz/UniFAR-FTUs huggingface dataset:
A technique for implantation of a 3-dimensional penetrating electrode array in the modiolar nerve of cats and humans.

BACKGROUND We believe that direct intraneural stimulation of the modiolar nerve using an array of electrodes will have lower thresholds, offer greater frequency selectivity and more stimulation sites, and have a greater frequency representation than conventional cochlear implants. OBJECTIVES To describe a potential auditory prosthesis based on electrical stimulation of the modiolar cochlear nerve and to report the development of a surgical approach in human and animal models. DESIGN Cadaveric human and animal studies conducted in temporal bones indicated that an array of penetrating microelectrodes could be implanted in the modiolar nerve. Cat studies using anesthesia were performed to develop the surgical procedure in an animal model. Nerve viability was assessed by measurement of electrically evoked auditory brainstem responses at different stages of the surgery. SUBJECTS Two fresh cadaveric human temporal bones, 3 cat cadavers, 1 pig cadaver, and 6 anesthetized cats were used in the experiments. RESULTS We were able to implant arrays containing 20 microelectrodes in the human modiolar nerve after exposure by a modified extended facial recess approach. In animals, the modiolar nerve was accessed by the transbulla and the middle fossa approach. The cat was chosen as the appropriate animal model, and the transbulla approach was selected. The round window was exposed by ventral access to the bulla and after cochleostomy; drilling the modiolar bone exposed the modiolar nerve. The mean +/- SD diameter of the exposed nerve in cats was 1.64 +/- 0.07 mm (n = 9), and the mean +/- SD exposed length was 2.50 +/- 0.11 mm (n = 9); this is adequate to accommodate 20 microelectrodes. The electrically evoked auditory brainstem responses indicated nerve survival during and after the surgery. CONCLUSIONS The surgical technique allows implantation of up to 20 microelectrodes in the cat and human modiolar nerve. The nerve survives the surgical procedure. This work enables studies in the electrophysiological properties and consequences of long-term implantation.
A comparative study of distillery spent wash with NPK (standard chemical fertilizers) at seedling stage of sorghum (Sorghum Bicolor L.)

The price of commercial chemical fertilizers is beyond the purchasing power of farming community of world’s developing countries. Therefore, to find out the substitute of these commercial chemical fertilizers a comparative study was conducted at seedling stage of sorghum variety named Sarokartuho in seed testing laboratory. The experiment was carried out in completely randomized design (CRD) with three replications and three treatments, i.e. only drinking water (as check), recommended dose of Nitrogen, Phosphorus, Potassium (NPK commercial fertilizer), 30%+70% of distillery spent wash + water, 50%+50% distillery spent wash + water respectively. The results for spent wash (T2) were at seed germination% (95.33%), shoot length (6.62 cm), root length (5.49 cm), shoot fresh weight (0.18 mg), root fresh weight (0.019 mg), shoot dry weight (0.017 mg) and root-dry weight (0.005 mg) of sorghum. However, the maximum values for these all traits of observations except seed germination were recorded at recommended dose of NPK (chemical fertilizers).
microRNA profiling between Bacillus thuringiensis Cry1Ab‐susceptible and ‐resistant European corn borer, Ostrinia nubilalis (Hübner)

Transgenic maize hybrids that express insecticidal Bacillus thuringiensis (Bt) crystalline (Cry) protein toxins effectively protect against the European corn borer, Ostrinia nubilalis, a devastating maize pest. Field monitoring and laboratory selections have detected varying levels of O. nubilalis resistance to Cry1Ab toxin. MicroRNAs (miRNAs) are short noncoding RNAs that are involved in post‐transcriptional gene regulation. Their potential roles in the evolution of Bt resistance, however, remain largely unknown. Sequencing of small RNA libraries from the midgut of Cry1Ab‐susceptible and resistant O. nubilalis larvae resulted in the discovery of 277 miRNAs, including 248 conserved and 29 novel. Comparative analyses of miRNA expression profiles between the laboratory strains predicted 26 and nine significantly up‐ and down‐regulated transcripts, respectively, in the midgut of Cry1Ab resistant larvae. Amongst 15 differentially regulated miRNAs examined by quantitative real‐time PCR, nine (60%) were validated as cosegregating with Cry1Ab resistance in a backcross progeny. Differentially expressed miRNAs were predicted to affect transcripts involved in cell membrane components with functions in metabolism and binding, and the putative Bt‐resistance genes aminopeptidase N and cadherin. These results lay the foundation for future investigation of the potential role of miRNAs in the evolution of Bt resistance.
Molecular pathology of lung cancer: current status and perspectives

Purpose of review In this article, we summarize the current knowledge on molecular alterations in lung cancer that are targets for therapy, and provide an outlook on the future development of molecular pathology in precision oncology. Recent findings Lung cancer has become a paradigm for the success of molecular targeted therapies in solid tumors. Tyrosine kinase inhibitors are effective treatment options in adenocarcinoma patients with an EGFR, ALK, ROS1 or B-Raf Proto-Oncogene, Serine/Threonine kinase mutation. Additional molecular targets that are addressed in clinical trials include ERBB2, MET, RET, NTRK1 and FGFR. Therapies with antibodies that block the interaction of PD-L1 with PD-1 and thereby liberate an antitumor immune response have introduced a new era in cancer therapy with impressive therapeutic benefits. The high financial burden, treatment failures and therapeutic side effects of immunotherapies have prompted a search for biomarkers beyond PD-L1 expression, for example, tumor mutation load or immune cell profiling, that might more reliably identify patients that are likely to respond. Summary The discoveries of cancer research have been translated into the clinical management of lung cancer patients. So far, the approach of targeted therapy that is directed towards certain molecular alterations in a given tumor has been successful for adenocarcinomas, but not yet for squamous or small cell carcinomas. Further clinical progress will require a better understanding of the molecular interactions within cancer cells that will subsequently enable innovative drug designs. Diagnostic molecular pathology will be a provider of information on a tumor's features and thus, navigate precision cancer therapy.
Hepatocyte-derived cysteinyl leukotrienes modulate vascular tone in experimental cirrhosis.

BACKGROUND & AIMS The leukotrienes C(4)/D(4)/E(4) (cysteinyl-LTs) are 5-lipoxygenase (5-LO)-derived eicosanoids with potent vasoconstrictor, proliferative, and profibrogenic properties that may participate in key pathophysiologic events in liver cirrhosis. We examined the cysteinyl-LT biosynthetic pathway in liver tissue and purified liver cells isolated from rats with carbon tetrachloride-induced cirrhosis, and assessed the vasoactive properties of LTD(4) in hepatic stellate cells (HSCs) and anesthetized rats. METHODS & RESULTS Liver homogenates from cirrhotic rats had increased 5-LO mRNA and cysteinyl-LT content, as determined by Northern blot and enzyme immunoassay, respectively. In isolated rat liver cells, 5-LO mRNA expression was found to be restricted to Kupffer cells. However, among the liver cells (i.e., hepatocytes, Kupffer cells, HSCs, and sinusoidal endothelial cells), hepatocytes exhibited the highest ability to generate cysteinyl-LTs from the unstable intermediate LTA(4). Hepatocytes from cirrhotic rats showed an enhanced baseline generation of cysteinyl-LTs, but their ability to synthesize cysteinyl-LTs from exogenous LTA(4) was found to be similar to that of hepatocytes from normal animals. Both LTD(4) and hepatocyte-conditioned medium increased intracellular Ca(2+) concentration and induced contraction in HSCs, suggesting that hepatocyte-derived cysteinyl-LTs could act in a paracrine fashion on nearby nonparenchymal liver cells. The relevance of these in vitro findings was further established in vivo by the observation that LTD(4) significantly increased portal pressure in anesthetized rats. CONCLUSIONS These data suggest a role for hepatocyte-derived cysteinyl-LTs in mediating hepatic vascular tone abnormalities in cirrhosis.
Management and treatment of osteoporosis in patients receiving long-term glucocorticoid treatment: current status of adherence to clinical guidelines and related factors.

OBJECTIVE The aim of this study was to evaluate the adherence of guidelines for the management and treatment of glucocorticoid-induced osteoporosis, and to investigate whether it is associated with factors such as age, gender, glucocorticoid dose, physician specialty, and size of facility. METHODS This was a cross-sectional study utilizing administrative data from a database of health insurance claims (2004-2007); 2,368 patients who received glucocorticoid treatment for ≥90 days were extracted. The guideline adherence was determined by evaluations based on glucocorticoid prescription dose, prescription of anti-osteoporosis drugs, and whether or not bone mineral density was measured. RESULTS Overall proportion of guideline adherence was 23.3%. In cases in which the equivalent dose of prednisolone was <5 mg/d and ≥5 mg/d, the adherence was 8.3% and 30.5% respectively. Factors correlating with low adherence included young age, male gender, and lower glucocorticoid doses. Surgery and otolaryngology specialties had lower adherence than internal medicine. Smaller clinical facilities had lower adherence than larger facilities. CONCLUSION The adherence of guidelines for the management and treatment of glucocorticoid-induced osteoporosis is still low, and improvements in treatment quality can be expected through education of patient groups and medical care providers with large deviations from the guidelines.
Effect of storage on levels of nitric oxide metabolites in platelet preparations

BACKGROUND: Nitric oxide (NO), a potent signaling molecule, is known to inhibit platelet (PLT) function in vivo. We investigated how the levels of NO and its metabolites change during routine PLT storage. We also tested whether the material of PLT storage containers affects nitrite content since many plastic materials are known to contain and release nitrite.
Effects of free wall ischemia and bundle branch block on systolic ventricular interaction in dog hearts.

Systolic direct ventricular interaction is thought to occur via the ventricular septum and the coordinated contraction of common fibers shared by both ventricles. The purpose of the present study was to evaluate the effects of transient free wall ischemia and bundle branch block, which disrupt the coordinated contraction of shared common fibers, on left-to-right systolic ventricular interaction. We produced transient right and left ventricular free wall ischemia by 2-min coronary artery occlusions and bundle branch block by ventricular pacing in nine in situ dog hearts. To eliminate any confounding effect of series interaction, we used an abrupt hemodynamic perturbation (aortic constriction), and we measured systolic interaction gain (IG) as delta right ventricular peak systolic pressure/delta left ventricular peak systolic pressure (IG(peak)) and instantaneous delta right ventricular pressure/delta left ventricular pressure at matched data sampling times (IG(inst)), along with changes in right ventricular stroke volume and stroke work before and on the beat immediately after the aortic constriction. To achieve equivalence of the interventricular septal pressure transmission contribution to ventricular interaction, the delta left ventricular peak systolic pressure produced by the aortic constriction was matched under all experimental conditions [average increase: 64 +/- 19 (SD) mmHg]. Control IG(peak) was 0.12 +/- 0.05, and control IG(inst) was 0.11 +/- 0.05. These values did not change with either free wall ischemia or ventricular pacing, with or without an intact pericardium. The changes in right ventricular stroke volume and stroke work produced by the aortic constriction were not different from zero, during either ischemia or ventricular pacing, with or without an intact pericardium. (ABSTRACT TRUNCATED AT 250 WORDS)
Implant-supported mandibular overdentures can minimize mandibular bone resorption in edentulous patients: results of a long-term radiologic evaluation.

PURPOSE It has been suggested that functional loading and light irritative stimuli could lead to changes in bone architecture, shape, and volume, and that by placing implants in the edentulous mandible and subsequently loading them, functional conditions could be created to limit bone resorption or even stimulate bone apposition (the latter was reported only for fixed implant-supported prosthetic reconstructions) in the distal area of the mandibular osseous crest. The aim of this study was to radiographically assess the bone height changes in the posterior area of the mandible after implant placement and loading with an overdenture on two or four implants over a mean follow-up period of 10.5 years. MATERIALS AND METHODS Panoramic radiographs were taken of 82 totally edentulous patients before implant placement and at repeated follow-up intervals spread over a mean observation time of 10.5 years. All patients received an implant-supported overdenture as prosthetic treatment. The mandibular bone height in the distal part of the mandible was measured on each of the available radiographs and the initial, intermediate, and final values were compared. RESULTS A mean mandibular bone height reduction of 0.5 mm was measured. CONCLUSION No clinically relevant difference was found between the posterior mandible height before implant placement and at follow-up after functional loading with an implant-supported mandibular overdenture.
Preparation, degradation, and calcification of biodegradable polyurethane foams for bone graft substitutes.

Autogenous cancellous bone graft is used to heal critical-size segmental long bone defects and defects in the maxillofacial skeleton. Harvesting of bone graft is traumatic, causes morbidity of the donor site, and often results in complications. Thus, there is a need for new biologically functional bone graft substitutes that, instead of autogenous bone graft, could be used to facilitate bone regeneration in critical-size defects. Porous biodegradable elastomeric polyurethane scaffolds combined with the patient's own bone marrow could potentially be such bone substitutes. The elastomeric bone substitute prevents shear forces at the interface between bone and rigid, e.g., ceramic bone substitutes and establishes an intimate contact with the native bone ends, thus facilitating the proliferation of osteogenic cells and bone regeneration. Crosslinked 3D biodegradable polyurethane scaffolds (foams) with controlled hydrophilicity for bone graft substitutes were synthesized from biocompatible reactants. The scaffolds had hydrophilic-to-hydrophobic content ratios of 70:30, 50:50, and 30:70. The reactants used were hexamethylene diisocyanate, poly(ethylene oxide) diol (MW = 600) (hydrophilic component), and poly(epsilon-caprolactone) diol (M(w) = 2000), amine-based polyol (M(w) = 515) or sucrose-based polyol (M(w) = 445) (hydrophobic component), water as the chain extender and foaming agent, and stannous octoate, dibutyltin dilaurate, ferric acetylacetonate, and zinc octoate as catalysts. Citric acid was used as a calcium complexing agent, calcium carbonate, glycerol phosphate calcium salt, and hydroxyapatite were used as inorganic fillers, and lecithin or solutions of vitamin D(3) were used as surfactants. The scaffolds had an open-pore structure with pores whose size and geometry depended on the material's chemical composition. The compressive strengths of the scaffolds were in the range of 4-340 kPa and the compressive moduli in the range of 9-1960 kPa, the values of which increased with increasing content of polycaprolactone. Of the two materials with the same amount of polycaprolactone the compressive strengths and moduli were higher for the one containing inorganic fillers. The scaffolds absorbed water and underwent controlled degradation in vitro. The amount of absorbed water and susceptibility to degradation increased with the increasing content of the polyethylene oxide segment in the polymer chain and the presence in the material of calcium complexing moiety. All polyurethane scaffolds induced the deposition of calcium phosphate crystals, the structure and calcium:phosphorus atomic ratio of which depended on the chemical composition of the polyurethane and varied from 1.52-2.0.
Development of multipurpose peroxisomes in Candida boidinii grown in oleic acid-methanol limited continuous cultures

We have studied the development and metabolic significance of peroxisomes in the yeast Candida boidinii following adaptation of the organism to cultivation conditions which require the simultaneous presence and activity of two independent peroxisome-mediated pathways for growth. After the addition of methanol to oleic acid-grown cells at late exponentional growth, a number of new small peroxisomes developed which, apart from the presence of beta-oxidation enzymes, were characterized by the presence of enzymes involved in methanol metabolism (alcohol oxidase and dihydroxyacetone synthase). The latter proteins, however, were absent in the larger organelles which were originally present in the oleic acid-grown cells prior to the addition of methanol and which contained only enzymes of the beta-oxidation pathway. Subsequent experiments on cells from continuous cultures grown on a mixture of oleic acid and methanol at steady-state conditions revealed that both the enzymes of the beta-oxidation pathway and those involved in methanol metabolism were found in one and the same compartment. Thus, under these conditions the cells contained peroxisomes which were concurrently involved in the metabolism of two different carbon sources simultaneously used for growth. Our results indicated that the heterogeneity in the peroxisomal population of a single cell, observed in the transient state following the addition of methanol, is only temporary and due to heterogeneity among these organelles with respect to their capacity to incorporate newly synthesized matrix proteins.
Habituation of Premonitory Sensations During Exposure and Response Prevention Treatment in Tourette's Syndrome

Exposure to premonitory sensations and response prevention of tics (ER) has been shown to be a promising new treatment for Tourette's syndrome (TS). The present study tested the hypothesis that habituation to unpleasant premonitory sensations associated with the tic is an underlying mechanism of change in ER. Patients rated the severity of sensations and urges at 15-minute intervals during ten 2-hour ER sessions. Multilevel models using multiple time trend analyses showed significant reductions of the sensory severity ratings both within and between sessions. The decrease of these severity ratings was related to the frequency of tics exhibited during sessions, regardless of tic severity at baseline. These results support the hypothesis that habituation may be at least part of the underlying working mechanism of exposure in the treatment of tics in TS and that effective tic suppression during sessions is an important factor in this habituation process.
Prediction of Destinations and Routes in Urban Trips with Automated Identification of Place Types and Stay Points

Predicting the destination and the route that someone is likely to take is useful for various purposes, such as to prevent people from going through congested routes. Most of existing approaches to this prediction problem only consider geographic patterns within their models, although this appears to be not enough for creating a robust predictor. This paper proposes an approach to improving the task of predicting route and destination which makes use of further semantic information associated with destinations and routes, apart from location patterns. Our model does not require user's active interaction and is able to automatically identify stay points (i.e., places users visit) and type of places. We evaluated our model with real world data collected from users' smartphones and obtained promising results.
Roles of CLOCK Phosphorylation in Suppression of E-Box-Dependent Transcription

ABSTRACT In mammalian circadian clockwork, the CLOCK-BMAL1 heterodimer activates E-box-dependent transcription, while its activity is suppressed by circadian binding with negative regulators, such as CRYs. Here, we found that the CLOCK protein is kept mostly in the phosphorylated form throughout the day and is partly hyperphosphorylated in the suppression phase of E-box-dependent transcription in the mouse liver and NIH 3T3 cells. Coexpression of CRY2 in NIH 3T3 cells inhibited the phosphorylation of CLOCK, whereas CIPC coexpression markedly stimulated phosphorylation, indicating that CLOCK phosphorylation is regulated by a combination of the negative regulators in the suppression phase. CLOCK-BMAL1 purified from the mouse liver was subjected to tandem mass spectrometry analysis, which identified Ser38, Ser42, and Ser427 as in vivo phosphorylation sites of CLOCK. Ser38Asp and Ser42Asp mutations of CLOCK additively and markedly weakened the transactivation activity of CLOCK-BMAL1, with downregulation of the nuclear amount of CLOCK and the DNA-binding activity. On the other hand, CLOCKΔ19, lacking the CIPC-binding domain, was far less phosphorylated and much more stabilized than wild-type CLOCK in vivo. Calyculin A treatment of cultured NIH 3T3 cells promoted CLOCK phosphorylation and facilitated its proteasomal degradation. Together, these results show that CLOCK phosphorylation contributes to the suppression of CLOCK-BMAL1-mediated transactivation through dual regulation: inhibition of CLOCK activity and promotion of its degradation.
Movement of the Na+ Channel Inactivation Gate during Inactivation*

Phenylalanine 1489 in the inactivation gate of the rat brain IIA sodium channel α subunit is required for stable inactivation. It is proposed to move into the intracellular mouth of the pore and occlude it during inactivation, but direct evidence for movement of this residue during inactivation has not been presented. We used the substituted cysteine accessibility method to test the availability of a cysteine residue substituted at position 1489 to modification by methanethiosulfonate reagents applied from the cytoplasmic side. Mutation of Phe-1489 to Cys results in a small (8%) fraction of noninactivating current. Ag+ and methanethiosulfonate reagents irreversibly slowed the inactivation rate and increased the fraction of noninactivating current of F1489C but not wild-type channels. Single channel analysis showed that modification slowed inactivation from both closed and open states and destabilized the inactivated state. Depolarization prevented rapid modification of Cys-1489 by these reagents, and the voltage dependence of their reaction rate correlated closely with steady-state inactivation. Modification was not detectably voltage-dependent at voltages more negative than channel gating. Our results show that, upon inactivation, Phe-1489 in the inactivation gate moves from an exposed and modifiable position outside the membrane electric field to a buried and inaccessible position, perhaps in or near the intracellular mouth of the channel pore.