Miracle-dz/UniFAR-FTUs huggingface dataset:
miR-34c-5p functions as pronociceptive microRNA in cancer pain by targeting Cav2.3 containing calcium channels

Abstract Pathophysiological mechanisms underlying pain associated with cancer are poorly understood. microRNAs (miRNAs) are a class of noncoding RNAs with emerging functional importance in chronic pain. In a genome-wide screen for miRNAs regulated in dorsal root ganglia (DRG) neurons in a mouse model of bone metastatic pain, we identified miR-34c-5p as a functionally important pronociceptive miRNA. Despite these functional insights and therapeutic potential for miR-34c-5p, its molecular mechanism of action in peripheral sensory neurons remains unknown. Here, we report the identification and validation of key target transcripts of miRNA-34c-5p. In-depth bioinformatics analyses revealed Cav2.3, P2rx6, Oprd1, and Oprm1 as high confidence putative targets for miRNA-34c-5p. Of these, canonical and reciprocal regulation of miR-34c-5p and Cav2.3 was observed in cultured sensory neurons as well as in DRG in vivo in mice with cancer pain. Coexpression of miR-34c-5p and Cav2.3 was observed in peptidergic and nonpeptidergic nociceptors, and luciferase reporter assays confirmed functional binding of miR-34c-5p to the 3′ UTR of Cav2.3 transcripts. Importantly, knocking down the expression of Cav2.3 specifically in DRG neurons led to hypersensitivity in mice. In summary, these results show that Cav2.3 is a novel mechanistic target for a key pronociceptive miRNA, miR-34c-5p, in the context of cancer pain and indicate an antinociceptive role for Cav2.3 in peripheral sensory neurons. The current study facilitates a deeper understanding of molecular mechanisms underlying cancer pain and suggests a potential for novel therapeutic strategies targeting miR-34c-5p and Cav2.3 in cancer pain.
Resistance to antibiotics and biocides among non-fermenting Gram-negative bacteria.

OBJECTIVE To investigate the antibiotic and biocide susceptibilities of clinical isolates of rarely encountered Gram-negative, non-fermenting bacteria. METHODS Thirty Gram-negative non-fermenting bacterial strains were isolated from blood cultures of oncology patients. These were studied for their resistance to 11 antibiotics. Their susceptibilities to seven biocides used in hospitals were also examined. RESULTS Isolates of Stenotrophomonas maltophilia and Ochrobactrum anthropi were generally resistant to at least five of the antibiotics, whereas isolates of Comamonas acidivorans, Flavobacterium oryzihabitans, Aeromonas hydrophila, Sphingobacterium spiritivorum, Acinetobacter junii and Acinetobacter lwoffi were generally sensitive to at least nine of the antibiotics. Trovafloxacin and trimethoprim-sulfamethoxazole were the most effective antibacterial agents tested, with 0% and 7%, respectively, of isolates being resistant, whereas 63% of isolates were resistant to aztreonam. Some isolates, sensitive to meropenem and/or ceftazidime in vitro, possessed very high MBC/MIC ratios for these beta-lactams. Two out of three biocides used in hospital pharmacies showed lethal activity towards all strains tested when used at less than one-third of their recommended in-use concentration. Proceine 40 failed to give a 5 log reduction in bacterial cell number for the isolates tested when used at its "in-use" concentration. A concentration of > 500 mg/L chlorhexidine was required to achieve a 5 log reduction for the same isolates. CONCLUSIONS We have examined the antibiotic susceptibilities of non-fermenting Gram-negative bacterial strains isolated from immunocompromised patients. Despite being sensitive to certain antibiotics in vitro, some isolates were still able to cause serious bacteremia. We have also reported for the first time the susceptibilities of non-fermenting Gram-negative bacteria to common biocides used in hospital infection control, and have shown that some strains are able to persist at the "in-use" concentration of particular biocides. It is therefore important to study further this particular group of organisms, and, in particular, to examine whether there exists a link between resistance to antibiotics and resistance to biocides.
Histomonas meleagridis and Capillarid Infection in a Captive Chukar (Alectoris chukar)

Abstract A female, adult, pen-raised chukar (Alectoris chukar) was submitted for postmortem examination. The main gross findings were severe emaciation, coelomic cavity and pericardial edema, and a large, sharply demarcated area of necrosis in the liver. Histologically, the liver lesions were characterized by areas of severe necrosis and inflammation containing numerous protozoal organisms morphologically consistent with Histomonas meleagridis. There was necrotizing typhlitis, with few histomonads and scant Heterakis spp. worms, in the cecum. Numerous aphasmid organisms, consistent with capillarids, were present in the crop and esophageal mucosa. Histomonas meleagridis was identified from frozen samples of liver by polymerase chain reaction and nucleotide sequencing. Sequence analysis of the internal transcribed spacer (ITS)-1, 5.8S, and ITS-2 regions of the ribosomal RNA gene disclosed a 95% identity to a previously sequenced ITS-1, 5.8S, and ITS-2 region of H. meleagridis.
Bone mass, bone mineral density and muscle mass in professional golfers

The aim of this study was to determine the effects of long-term professional golf participation on whole-body and regional bone mass and density. Dual-energy X-ray absorptiometry was performed on 15 male professional golfers and 18 sedentary individuals, matched for sex, race, age (29 ± and 25 ± 1 years, respectively), body mass (79 ± 2 and 74 ± 2 kg), height (1.78 ± 0.01 and 1.77 ± 0.02 m) and percent body fat (20 ± 2 and 21 ± 2%; mean ± s χ). We found that long-term professional golf participation is not associated with significant increments in regional or whole-body bone mass or density. Neither the lumbar spine nor the femoral neck showed any noticeable enhancement of bone mass in professional golfers compared with controls from the same population. The only effect of professional golf participation on regional body composition was a 9% increase in muscle mass in the dominant arm (P ≪ 0.05).
Identification of the cytochrome P450 enzymes involved in the N-demethylation of sildenafil.

AIMS To characterize the cytochrome P450 (CYP) enzymes responsible for the N-demethylation of sildenafil to its main metabolite, UK-103 320, to investigate the potential inhibitory effects of sildenafil on CYP enzymes and to evaluate the potential of selected drugs to affect sildenafil metabolism. METHODS The metabolic pathways of sildenafil N-demethylation were studied using human liver microsomes, as well as microsomes expressing individual human CYP enzymes. Further studies to identify the individual enzymes were performed at 2.5 and 250 microM sildenafil, and employed a combination of chemical inhibition, correlation analysis, and metabolism by expressed recombinant CYP enzymes. In addition, the effect of sildenafil on the activity of the six major drug metabolizing enzymes was investigated. RESULTS Sildenafil conversion was found to be mediated by at least two CYP enzymes, for which the mean kinetic parameters were Km1 = 6(+/-3 microM), Km2 = 81(+/-45 microM), Vmax1 = 22(+/-9 pmol) and Vmax2 = 138(+/-77 pmol) UK-103 320 formed min(-1) mg(-1). At 250 microM sildenafil, N-demethylation was primarily mediated through the low-affinity, high-Km enzyme (approximately 83%), whilst at 2.5 microM there was a greater role for the high-affinity, low-Km enzyme (approximately 61%). Ketoconazole strongly inhibited metabolism at both sildenafil concentrations and was the only significant inhibitor at 250 microM sildenafil. At the lower sildenafil concentration, sulphaphenazole and quinidine also inhibited formation of UK-103 320. Overall, 75% or more of the N-demethylation of sildenafil at any concentration is probably attributable to CYP3A4. These results were supported by experiments using expressed human CYP enzymes, in which only CYP3A4 and CYP2C9 exhibited substantial sildenafil N-demethylase activity (respective Km values of 221 microM and 27 microM). Sildenafil metabolism was inhibited by potent CYP3A4 inhibitors which are used clinically, but was found to be only a weak inhibitor of drug metabolizing enzymes itself, the strongest inhibition occurring against CYP2C9 (Ki = 80 microM). CONCLUSIONS Evidence is provided for CYP3A4 and to a lesser extent CYP2C9-mediated metabolism of sildenafil. There is the possibility that elevated plasma concentrations of sildenafil could occur with coadministration of known inhibitors of CYP2C9 or CYP3A4. Since peak plasma concentrations of clinical doses of sildenafil are only 200 ng ml(-1) ( approximately 0.4 microM) it is very unlikely that sildenafil will significantly alter the plasma concentration of other compounds metabolized by cytochrome P450 enzymes.
The C-Terminal 88 Amino Acids of the Sendai Virus P Protein Have Multiple Functions Separable by Mutation

ABSTRACT The Sendai virus P-L polymerase complex binds the NP-encapsidated nucleocapsid (NC) template through a P-NP interaction. To identify P amino acids responsible for binding we performed site-directed mutagenesis on the C-terminal 88 amino acids in the NC binding domain. The mutant P proteins expressed from plasmids were assayed for viral RNA synthesis and for various protein-protein interactions. All the mutants formed P oligomers and bound to L protein. While two mutants, JT3 and JT8, retained all P functions at or near the levels of wild-type (wt) P, three others—JT4, JT6, and JT9—were completely defective for both transcription and genome replication in vitro. Each of the inactive mutants retained significant NC binding but had a different spectrum of other binding interactions and activities, suggesting that the NC binding domain also affects the catalytic function of the polymerase. NC binding was inhibited by combinations of the inactive mutations. The remaining P mutants were active in transcription but defective in various aspects of genome replication. Some P mutants were defective in NP0 binding and abolished the reconstitution of replication from separate P-L and NP0-P complexes. In some of these cases the coexpression of the wt polymerase with the mutant NP0-P complex could rescue the defect in replication, suggesting an interaction between these complexes. For some P mutants replication occurred in vivo, but not in vitro, suggesting that the intact cell is providing an unknown function that cannot be reproduced in extracts of cells. Thus, the C-terminal region of P is complex and possesses multiple functions besides NC binding that can be separated by mutation.
Power aware cache miss reduction by energy efficient victim retention

Most of the chip-multiprocessors share a large sized last level cache(LLC) which is divided into multiple banks in NUCA based architectures. Recent study on LLC power consumption indicates that, LLC consumes principal amount of chip power. The LLC power consumption can be divided into two major parts: dynamic power and static power. Techniques have been proposed to reduce static power by powering off some less utilized cache portions. But, powering off some cache portion can degrade the system performance. In this paper, we reduce the cache power consumption by shutting down some cache ways of less utilized cache sets and then apply victim retention(VR) technique in the remaining portion to reduce cache misses. Experimental analysis shows 35% reduction in static power and 11.31% reduction in EDP, on an average for a 2MB LLC with negligible change in performance.
Performance evaluation of the MiniMed continuous glucose monitoring system during patient home use.

BACKGROUND The recent availability of a continuous glucose monitor offers the opportunity to match the demands of intensive diabetes management with a period of equally intensive blood glucose monitoring. The present study evaluates the performance of the MiniMed continuous glucose monitoring system (CGMS) in patients with diabetes during home use. METHODS Performance data and demographic information were obtained from 135 patients who were (mean +/- SD) 40.5+/-14.5 years old, had an average duration of diabetes of 18.0+/-9.8 years, 50% were female, 90% were Caucasian, and 87% of whom had been diagnosed with type 1 diabetes. Patients were selected by their physician, trained on the use of the CGMS and wore the device at home for 3 days or more. The performance of the CGMS was evaluated against blood glucose measurements obtained using each patient's home blood glucose meter. Evaluation statistics included correlation, linear regression, mean difference and percent absolute difference scores, and Clarke error grid analysis. RESULTS The CGMS values were compared to 2477 SMBG tests (r = 0.91, slope = 0.93, intercept = 14.5 mg/dL, mean absolute difference = 18.0%+/-19.8%). Clarke error grid analysis showed 96.2% of the data pairs falling within the clinically acceptable regions (zones A and B). CONCLUSIONS These results demonstrate the agreement of the CGMS to blood glucose meter values, under conditions of home use, in patients selected by their physicians as candidates for continuous monitoring. The detailed glucose information provided by the CGMS should make successful management of diabetes more easily achieved.
Stable phantom materials for ultrasound and optical imaging

Phantoms mimicking the specific properties of biological tissues are essential to fully characterize medical devices. Water-based materials are commonly used to manufacture phantoms for ultrasound and optical imaging techniques. However, these materials have disadvantages, such as easy degradation and low temporal stability. In this study, we propose an oil-based new tissue-mimicking material for ultrasound and optical imaging, with the advantage of presenting low temporal degradation. A styrene-ethylene/butylene-styrene (SEBS) copolymer in mineral oil samples was made varying the SEBS concentration between 5%–15%, and low-density polyethylene (LDPE) between 0%−9%. Acoustic properties, such as the speed of sound and the attenuation coefficient, were obtained using frequencies ranging from 1–10 MHz, and were consistent with that of soft tissues. These properties were controlled varying SEBS and LDPE concentration. To characterize the optical properties of the samples, the diffuse reflectance and transmittance were measured. Scattering and absorption coefficients ranging from 400 nm–1200 nm were calculated for each compound. SEBS gels are a translucent material presenting low optical absorption and scattering coefficients in the visible region of the spectrum, but the presence of LDPE increased the turbidity. Adding LDPE increased the absorption and scattering of the phantom materials. Ultrasound and photoacoustic images of a heterogeneous phantom made of LDPE/SEBS containing a spherical inclusion were obtained. Annatto dye was added to the inclusion to enhance the optical absorbance. The results suggest that copolymer gels are promising for ultrasound and optical imaging, making them also potentially useful for photoacoustic imaging.
Paramagnetic Lanthanide(III) complexes as pH‐sensitive chemical exchange saturation transfer (CEST) contrast agents for MRI applications

The recently introduced new class of contrast agents (CAs) based on chemical exchange saturation transfer (CEST) may have a huge potential for the development of novel applications in the field of MRI. In this work we explored the CEST properties of a series of Lanthanide(III) complexes (Ln = Eu, Dy, Ho, Er, Tm, Yb) with the macrocyclic DOTAM‐Gly ligand, which is the tetraglycineamide derivative of DOTA (1,4,7,10‐tetraazacyclododecane‐1,4,7,10‐tetraacetic acid). These complexes possess two pools of exchangeable protons represented by the coordinated water and the amide protons. Yb‐DOTAM‐Gly displays the most interesting CEST properties when its amide N‐H resonance (16 ppm upfield H2O signal) is irradiated. Up to 70% suppression of the water signal is obtained at pH 8. As the exchange rate of amide protons is base‐catalyzed, Yb‐DOTAM‐Gly results to be an efficient pH‐responsive probe in the 5.5–8.1 pH range. Moreover, a ratiometric method has been set up in order to remove the dependence of the observed pH responsiveness from the absolute concentration of the paramagnetic agent. In fact, the use of a mixture of Eu‐DOTAM‐Gly and Yb‐DOTAM‐Gly, whose exchangeable proton pools are represented by the coordinated water (ca. 40 ppm downfield H2O signal at 312K) and amide protons, respectively, produces a pH‐dependent CEST effect which is the function of the concentration ratio of the two complexes. Magn Reson Med 47:639–648, 2002. © 2002 Wiley‐Liss, Inc.
A Direct Speech-to-Speech Neural Network Methodology for Spanish-English Translation

In this work, a novel direct speech-to-speech methodology for translation is proposed; it is based on an LSTM neural network structure which has proven useful for translation in the classical way, i.e., the one consisting of three stages: speech-to-text conversion, text-to-text translation, and text-to-speech synthesis. In contrast with traditional approaches, the one in this work belongs to the recently appeared idea of direct translation without text representation, as this sort of training better corresponds to the way oral language learning takes place in humans. As a proof of concept digits are translated from an audio source in Spanish and pronounced as an audio signal in English. Advantages and disadvantages of the proposal when compared with traditional methodologies are discussed.
How are Azathioprine and 6‐mercaptopurine dosed by gastroenterologists? Results of a survey of clinical practice

Background: Azathioprine (AZA) and 6‐mercaptopurine (6‐MP) are accepted as effective therapy for Crohn's disease and ulcerative colitis. Although general guidelines have been suggested for weight‐based dosing of thiopurines, no standard of care has been established. Clinical trials have demonstrated efficacy for weight‐based dosing of AZA at 2.5 mg/kg/day and 6‐MP at 1.5 mg/kg/day. Escalation of dosing is recommended within 2 weeks of initiating therapy. The aim was to determine the prescribing practices of community practice gastroenterologists with respect to 6‐MP/AZA dosing. Methods: Questionnaires were distributed via a mail database or during gastroenterology society meetings to gastroenterologists in NY, NJ, and CT. Questionnaires ascertained starting doses of AZA/6‐MP, use of thiopurine methyltransferase (TPMT) enzyme testing, and strategy for dose optimization. Results: A total of 145 questionnaires were collected. Twenty‐four percent of gastroenterologists escalated the dose within 2 weeks after initiating therapy. The majority used weight‐based dosing as their target of therapy. Thirty‐five percent reported measuring TPMT levels and 46% used metabolite monitoring. Conclusions: Most gastroenterologists take longer than recommended to raise the dose of AZA/6‐MP. Although the majority of gastroenterologists reported maximal dosages based on weight, there may be a delay in achieving this goal. Optimizing dosing of AZA/6‐MP may improve efficacy and reduce the need to use additional therapy.
PS-1 SAW RFID Tag with Reduced Size

Surface acoustic wave (SAW) -based radio-frequency identification (RFID) tags are soon expected to be produced in very high volumes. The size and cost of a SAW RFID tag will be key parameters for many applications. Therefore, it is of primary importance to reduce the chip size. However, the number of distinct codes to be realized and the used frequency band impose limitations on the delays of coded responses and, consequently, on the tag size. The coded signal should arrive at the reader with a certain delay, that is, after the reception of the environmental echoes. An adequate initial delay is typically about 1 mus. If the tag uses a bidirectional interdigital transducer (IDT), the initial delay is needed on both sides of the IDT. In this work, we have replaced the bidirectional IDT by a unidirectional IDT. This allows to halve the space required by the initial delay, since all the reflectors must now be placed on the same side of the IDT. We have reduced the tag size even further by using a Z-path geometry with two strong inclined reflectors. In this configuration, the same space in the x-direction (the initial propagation direction) is used for both the initial delay and the code reflectors, which means that the chip length is finally determined only by the space required by the code reflectors. In this way, the tag length is reduced by about 2 mm compared to an equivalent single-track configuration using a unidirectional IDT with the code reflectors placed in line. The proposed configuration is especially advantageous for tags having a relatively long initial delay compared to the space required by the code reflectors. For such devices, a chip size of less than 2 mm by 1 mm (at 2.45 GHz) is realizable
Documented Intraoperative Hypotension According to the Three Most Common Definitions Does Not Match the Application of Antihypotensive Medication

This observational study investigated which of the three most common definitions of intraoperative hypotension (IOH), reported in a published systematic literature review, were associated best with anaesthetists' administration of antihypo-tensive medication (AHM). IOH and AHM use in anaesthetic procedures in a mixed surgical population (n = 2350) were also reviewed. The definitions were: arterial systolic blood pressure (SBP) < 100 mmHg or a fall in SBP of > 30% of the preoperative SBP baseline; arterial SBP < 80 mmHg; a fall in SBP of > 20% of the preoperative SBP. Accuracy of predicting AHM using these three definitions was 67%, 54% and 65%, respectively. Prediction by a new fourth definition, using an optimal threshold of minimal SBP falling to < 92 mmHg or by > 24% of preoperative baseline, was 68% accurate. In multivariate logistic analysis, age, volatile versus intravenous anaesthetics, medical history of arterial hypertension and all four definitions of IOH were associated with intraoperative AHM, however IOH was not associated with postoperative in-patient stay. The three original definitions correlated poorly with the anaesthetist's judgement about applying AHM. Anaesthetists make complex decisions regarding the relevance of IOH, considering various perioperative factors in addition to SBP. Age, physical status and duration and type of surgery showed better correlations with postoperative in-patient stay than IOH.