Miracle-dz/UniFAR-FTUs huggingface dataset:
Identification of Novel Targets of Immunosuppressive Agents by cDNA-based Microarray Analysis*

The immunosuppressive agents cyclosporin A (CsA) and tacrolimus (FK506) bind to unrelated intracellular immunophilin receptors, cyclophilin (CyP) and FK506-binding protein (FKBP), respectively. The complexes of CsA·CyP and of FK506·FKBP both bind to and inhibit the activity of the calcium/calmodulin-dependent serine/threonine phosphatase calcineurin. We used cDNA microarray analysis to characterize early human peripheral blood T cell transcriptional responses following antigen receptor stimulation in the absence or presence of CsA or FK506, hoping to identify novel targets dependent upon calcineurin or immunophilins or, perhaps, specific targets of either CyP or FKBP inhibitable by one drug alone. The array data failed to identify genes uniquely sensitive to only one drug, suggesting that transcriptionally regulated, immunophilin-dependent but calcineurin-independent targets fell below the limits of detection in this system. In contrast, transcript profiling identified and mRNA and protein analysis confirmed novel as well as known genes reproducibly induced or inhibited by both immunosuppressive agents. In this context, we show that transcriptional activation of Stat5a and repression of the cytokine interleukin-16 are regulated by T cell receptor engagement and dependent upon drug-immunophilin complexes and, presumably, calcineurin activity.
Minimally invasive fluoroscopic percutaneous peritoneal dialysis catheter salvage

Background Peritoneal dialysis catheter (PDC) dysfunction can often be treated fluoroscopically by manipulation with wire, balloon or stiff stylet, saving surgical intervention for refractory cases. We describe an enhanced percutaneous approach to PDC salvage that can lead to a more definitive intervention and salvage for cases refractory to fluoroscopic manipulation. Methods In five cases of PD catheter malfunction, the deep cuff was dissected free after a 0.035 hydrophilic wire was passed into the peritoneum through the PDC. Only the intraperitoneal portion of the PDC was explanted. The PDC was cleared of obstruction and omentum. The intraperitoneal portion of the PDC was reimplanted over wire via a peel-away sheath and the deep cuff sutured. Results Omental entrapment was present in three of five patients and fibrin occlusion in four of the five cases. All catheters were repaired successfully by the described technique. Post procedure, 3–5 days of lower volume, recumbent PD exchanges were performed prior to full-dose PD. No perioperative complications or leaks were noted. All PDCs were patent at 6 months. One patient required laparoscopy for recurrent omental wrapping 3 months post intervention. Conclusions PDC salvage in this manner is a cost-effective alternative to laparoscopic repair of PDCs failing catheter manipulation. The infection barrier afforded by the original superficial cuff and subcutaneous tunnel is maintained. PD can be resumed immediately. Only refractory cases need laparoscopy. This procedure allows for a more definitive correction of catheter migration and obstruction, avoids placement of a new PDC or temporary hemodialysis, is cost-effective and expands percutaneous options for dysfunctional PD catheters.
Impaired Virulence and Fitness of a Colistin-Resistant Clinical Isolate of Acinetobacter baumannii in a Rat Model of Pneumonia

ABSTRACT We compared the fitness and lung pathogenicity of two isogenic clinical isolates of Acinetobacter baumannii, one resistant (ABCR) and the other susceptible (ABCS) to colistin. In vitro, ABCR exhibited slower growth kinetics than ABCS. In a rat model of pneumonia, ABCR was associated with less pronounced signs of infection (lung bacterial count, systemic dissemination, and lung damage) and a better outcome (ABCR and ABCS mortality rates, 20 and 50%, respectively [P = 0.03]).
Transcriptome Analysis of the Oriental River Prawn, Macrobrachium nipponense Using 454 Pyrosequencing for Discovery of Genes and Markers

Background The oriental river prawn, Macrobrachium nipponense, is an economically and nutritionally important species of the Palaemonidae family of decapod crustaceans. To date, the sequencing of its whole genome is unavailable as a non-model organism. Transcriptomic information is also scarce for this species. In this study, we performed de novo transcriptome sequencing to produce the first comprehensive expressed sequence tag (EST) dataset for M. nipponense using high-throughput sequencing technologies. Methodology and Principal Findings Total RNA was isolated from eyestalk, gill, heart, ovary, testis, hepatopancreas, muscle, and embryos at the cleavage, gastrula, nauplius and zoea stages. Equal quantities of RNA from each tissue and stage were pooled to construct a cDNA library. Using 454 pyrosequencing technology, we generated a total of 984,204 high quality reads (338.59Mb) with an average length of 344 bp. Clustering and assembly of these reads produced a non-redundant set of 81,411 unique sequences, comprising 42,551 contigs and 38,860 singletons. All of the unique sequences were involved in the molecular function (30,425), cellular component (44,112) and biological process (67,679) categories by GO analysis. Potential genes and their functions were predicted by KEGG pathway mapping and COG analysis. Based on our sequence analysis and published literature, many putative genes involved in sex determination, including DMRT1, FTZ-F1, FOXL2, FEM1 and other potentially important candidate genes, were identified for the first time in this prawn. Furthermore, 6,689 SSRs and 18,107 high-confidence SNPs were identified in this EST dataset. Conclusions The transcriptome provides an invaluable new data for a functional genomics resource and future biological research in M. nipponense. The molecular markers identified in this study will provide a material basis for future genetic linkage and quantitative trait loci analyses, and will be essential for accelerating aquaculture breeding programs with this species.
Parent report of child's health-related quality of life after a primary-care-based weight management program.

BACKGROUND Health-related quality of life (HRQoL) has been recognized as an important target and health outcome in obesity research. The current study aimed to examine HRQoL in overweight or obese children after a 10-week primary-care-based weight management program, Parent-Led Activity and Nutrition for Healthy Living, in southern Appalachia. METHODS Sixty-seven children (ages 5-12 years) and their caregivers were recruited from four primary care clinics, two of which were randomized to receive the intervention. Caregivers in the intervention groups received two brief motivational interviewing visits and four group sessions led by providers as well as four phone follow-ups with research staff. Caregivers completed the PedsQL and demographic questionnaires at baseline and at 3, 6, and 12 months postintervention. Child height and weight were collected to determine standardized BMI. RESULTS Caregivers of children receiving the weight control intervention reported no statistically significant improvements in child total HRQoL, as compared to the control group, across the course of treatment (β=0.178; 95% confidence interval, -0.681, 1.037; p=0.687). Additionally, no statistically significant improvements were found across other HRQoL domains. CONCLUSIONS Future studies examining HRQoL outcomes in primary care may consider treatment dose as well as methodological factors, such as utilization of multiple informants and different measures, when designing studies and interpreting outcomes.
Early central atrophy rate predicts 5 year clinical outcome in multiple sclerosis

Objective To examine the predictive value of central atrophy in early multiple sclerosis (MS) patients, for medium term clinical outcome. Methods In 54 patients with recently diagnosed MS, clinical and MRI parameters were obtained at baseline, and after 2 and 5.5 years of follow-up. In addition to conventional MRI parameters and the annualised percentage brain volume change (aPBVC), the annualised percentage ventricular volume change (aPVVC) was quantified. Main outcome measure was disease progression, defined by an increase in Expanded Disability Status Scale of ≥1 after 5.5 years. Results Disease progression occurred in 29 patients. aPVVC within the first two years was significantly higher in these progressing patients (median 4.76%; IQR 3.05–9.17) compared with stable patients (median 3.23%; IQR −0.1–6.02) (p=0.02). A logistic regression model selected aPVVC within the first 2 years as the only MRI marker predicting progression after 5.5 years (OR 1.17, 95% CI 1.02 to 1.35). When entering all MRI and clinical markers, again aPVVC within the first 2 years was the only MRI marker selected. While aPVVC was correlated between the two consecutive time intervals (ρ=0.41, p<0.01), aPBVC was not. Furthermore, baseline T2 lesion load and gadolinium enhancing lesion load were correlated with aPVVC in the second time interval (2–5.5 years) but not with aPBVC. Conclusion The rate of ventricular enlargement seems to be even more strongly predictive of disease progression after medium term follow-up than whole brain atrophy rate, and also outperforms lesion measures. Central atrophy rate could therefore be an important prognostic marker, especially in the early stages of MS.
Line and Word Matching in Old Documents

This paper is concerned with the problem of establishing an index based on word matching. It is assumed that the book was digitised as better as possible and some pre-processing techniques were already applied as line orientation correction and some noise removal. However two main factor are responsible for being not possible to apply ordinary optical character recognition techniques (OCR): the presence of antique fonts and the degraded state of many characters due to unrecoverable original time degradation. In this paper we make a short introduction to word segmentation that involves finding the lines that characterise a word. After we discuss different approaches for word matching and how they can be combined to obtain an ordered list for candidate words for the matching. This discussion will be illustrated by examples.
S 1 Appendix

1. I feel tense or 'wound up'. (A) 2. I still enjoy the things I used to enjoy. (D) 3. I get a sort of frightened feeling as if something awful is about to happen. (A) 4. I can laugh and see the funny side of things. (D) 5. Worrying thoughts go through my mind. (A) 6. I feel cheerful. (D) 7. I can sit at ease and feel relaxed. (A) 8. I feel as if I am slowed down. (D) 9. I get a sort of frightened feeling like 'butterflies' in the stomach. (A) 10. I have lost interest in my appearance. (D) 11. I feel restless as I have to be on the move. (A) 12. I look forward with enjoyment to things. (D) 13. I get sudden feelings of panic. (A) 14. I can enjoy a good book or radio or TV program. (D)
Pelvic nerve plexus trauma at radical hysterectomy and simple hysterectomy

A major cause of the pelvic morbidity after a radical hysterectomy (RH) is thought to be damage to the pelvic nerve plexus, but direct evidence is lacking. We set out to determine the nerve content of the uterosacral ligaments (USLs) and cardinal ligaments (CLs) at the level at which they are divided during a radical hysterectomy and a simple hysterectomy.
Molecular and Susceptibility Analysis of Toxigenic Clostridium difficile Obtained from Adult Patients Suspected of CDI in Trinidad

Clostridium difficile is a Gram positive rod-shaped bacterium that produces two major toxins, A and B. The detection of the organism and its toxins has been widely carried out using specialized Enzyme-Linked Immunosorbent Assay (ELISA) kits; however these generally have been unsuccessful in identifying all Clostridium difficile positive samples. In this study, fifteen clinically symptomatic patients from three of the five major regional hospitals in Trinidad were investigated for Clostridium difficile infections. Stool samples were assessed by ELISA and cultured isolates were characterized using agar dilution antibiotic sensitivity assays, conventional Polymerase Chain Reaction (PCR), DNA sequencing and phylogenetic analysis of toxin A and B genes. All 15 patient stool samples and isolates were positive for toxigenic Clostridium difficile via ELISA and PCR respectively. All isolates were positive for the housekeeping tpi and Toxin B genes by PCR but only three of these were positive for the Toxin A gene. The Toxin B gene sequences showed 100% similarity levels among isolates while the Toxin A gene sequences showed 99% similarity among isolates. Phylogenetic analysis showed that the strains isolated in Trinidad most likely belonged to the same strain/group. Agar dilution sensitivity tests showed highest susceptibility to Pipercillin/Tazobactam and Meropenem (87%) and the highest resistance was seen with Cefotaxime in 93%. These results indicate that similar virulent strains of C. difficile are present in the Trinidad population and that pathogenic strains are more likely to be susceptible to Pipercillin/Tazobactam and Meropenem.
BioGlue: Albumin/Glutaraldehyde Sealant in Cardiac Surgery

Abstract BioGlue is a commercially available sealant manufactured by Cryolife (Atlanta, GA) as a hemostatic adjunct for cardiac and vascular surgery. This type of sealant has evolved conceptually from the gelatin resorcinol formalin glue (GRF or “French Glue”) in the sense that it is devised not only to act a sealant but also as an agent to strengthen friable tissues, particularly in acute aortic dissection. In fact, the initial availability of BioGlue in the United States was under an FDA humanitarian device exemption for use in acute aortic dissection. This novel regulatory strategy expedited clinical use of BioGlue in acute aortic dissection and was permissible because of the small number of patients (less than 4000 per annum) in the potential treatment population. In this article, we will discuss the mechanism of action and composition of this agent, preclinical experience, the results of a prospective randomized trial as well as the results of our initial experience with BioGlue at MGH. (J Card Surg 2003;18:500‐503)
Intrinsically Disordered Side of the Zika Virus Proteome

Over the last few decades, concepts of protein intrinsic disorder have been implicated in different biological processes. Recent studies have suggested that intrinsically disordered proteins (IDPs) provide structural plasticity and functional diversity to viral proteins that are involved in rapid replication and immune evasion in host cells. In case of Zika virus, the roles of protein intrinsic disorder in mechanisms of pathogenesis are not completely understood. In this study, we have analyzed the prevalence of intrinsic disorder in Zika virus proteome (strain MR 766). Our analyses revealed that Zika virus polyprotein is enriched with intrinsically disordered protein regions (IDPRs) and this finding is consistent with previous reports on the involvement of IDPs in shell formation and virulence of the Flaviviridae family. We found abundant IDPRs in Capsid, NS2B, NS3, NS4A, and NS5 proteins that are involved in mature particle formation and replication. In our view, the intrinsic disorder-focused analysis of ZIKV proteins could be important for the development of disorder-based drugs.
Specific receptors of the steroid hormones in breast cancer.

Interference with the endogenous production of estrogens has been shown to be an effective palliative therapy for mammary cancer in 20-45% of cases. Additive hormone therapy has also been used as an effective palliative measure. The characteristic of some estrogen target cells with the capacity to bind estradiol-17beta specifically and with high affinity to estrogen-binding protein or "estrogen-receptors" has been shown. This reaction is a sequential process. The steroid 1st enters the target cell and combines with a cytoplasmic form of receptor protein. The hormone-receptor complex undergoes a transformation and then translocates into the nucleur where it binds to acceptor sites presumably in the chromatin of the target cell. The nuclear form of the receptor requires the presence of estradiol. Sucrose gradient centrifugation showed 2 steroid binding proteins sedimenting at 8-9S and 4-5S. The significance of the distribution of the 8-9S and 4-5S receptor species in human breast tumors is not known. About 50% of all breast carcinomas contain specific estrogen receptors. The amount of receptor varies from tumor to tumor. Histologic features of the cancers do not explain the variation in levels of estrogen receptors. The cellular composition of a breast tumor may also include estrogen-independent cells. Remissions after hormone manipulations have occurred in a majority of patients with estrogen receptors (44 of 56 in the authors cases). A few (5 of 80) patients with tumors lacking estrogen receptors have experienced remissions following endocrine therapy. More rigid quantitation of estrogen receptors correlated with clinical response may improve the predictive usefulness of receptor information.
Diaphragmatic movement in hemiplegic patients measured by ultrasonography.

BACKGROUND--It is known that automatic breathing is controlled by centres in the lower brain stem, whereas volitional breathing is controlled by the cerebral cortical centres. In hemiplegia, lesions above the brain stem result in paralysis of limb muscles. This study was performed to determine whether the diaphragm might also be affected in patients with hemiplegia. METHODS--Studies were performed in six normal control subjects and in eight patients with complete hemiplegia caused by a lesion above the brain stem, all with no known chest disease. Full lung function tests were performed. Diaphragmatic excursion and inspired volume (VT) were measured simultaneously by M mode ultrasonography and respiratory airflow measurements. Recordings of diaphragmatic excursion were performed on each side separately during volitional and automatic breathing at a similar range of VT. RESULTS--Lung function tests lay within the normal range in all the control subjects. In the hemiplegic patients mean (SD) vital capacity was 79 (18)% and residual volume was 123(30)% of predicted. Total lung capacity and functional residual capacity were in the normal range. In the control subjects no significant difference in diaphragmatic excursion was found between volitional and automatic breathing for the same range of inspired volume. By contrast, there was a significant decrease in diaphragmatic excursion during volitional breathing compared with automatic breathing on the affected side in four of the eight hemiplegic patients. CONCLUSIONS--In four of eight hemiplegic patients reduced diaphragmatic movement was present on the paralysed side during volitional inspiration when compared with automatic inspiration. The hemidiaphragm may be involved on the affected side in patients with hemiplegia.
Diffusion of an integrated health education program in an urban school system: planet health.

OBJECTIVE Assessed the feasibility, acceptability, and sustainability of Planet Health, an interdisciplinary, integrated health education curriculum implemented in six public middle schools. METHODS Workshops on Planet Health implementation were attended by 129 teachers (language arts, math, science, and social studies) over three school years (1999-2000, 2000-2001, and 2001-2002). Questionnaires were administered post-implementation and in the fall and spring of each year. Outcomes were dose, acceptability, feasibility, and intent to continue use. RESULTS The average number of lessons taught per teacher per year was 1.7 to 3.1, compared to a goal of 2 to 3. Each year, teachers reported high acceptability and perceived feasibility of the intervention, and the majority indicated they intended to continue using the curriculum. CONCLUSIONS Planet Health was feasible and acceptable in a participatory research model involving a public school-university partnership, and it was also sustainable independent of the research effort.
Lactate as a Metabolite and a Regulator in the Central Nervous System

More than two hundred years after its discovery, lactate still remains an intriguing molecule. Considered for a long time as a waste product of metabolism and the culprit behind muscular fatigue, it was then recognized as an important fuel for many cells. In particular, in the nervous system, it has been proposed that lactate, released by astrocytes in response to neuronal activation, is taken up by neurons, oxidized to pyruvate and used for synthesizing acetyl-CoA to be used for the tricarboxylic acid cycle. More recently, in addition to this metabolic role, the discovery of a specific receptor prompted a reconsideration of its role, and lactate is now seen as a sort of hormone, even involved in processes as complex as memory formation and neuroprotection. As a matter of fact, exercise offers many benefits for our organisms, and seems to delay brain aging and neurodegeneration. Now, exercise induces the production and release of lactate into the blood which can reach the liver, the heart, and also the brain. Can lactate be a beneficial molecule produced during exercise, and offer neuroprotection? In this review, we summarize what we have known on lactate, discussing the roles that have been attributed to this molecule over time.
Predicting methane production in dairy cows

Methane is a potent greenhouse gas, to which enteric fermentation from ruminants contributes significantly. Reliable and accurate predictions of methane (CH₄) production from dairy cows would be of interest to develop mitigation strategies and for national inventories. Thus, the overall aim of this thesis was to predict CH₄ production in dairy cows by modelling approaches. Predicted in vivo CH₄ production decreased with increased sample size in the gas in vitro system. Molar proportion of acetate decreased at the expense of propionate. Digestibility also decreased with increased sample size. Predicted CH₄ production based on stoichiometric equations of volatile fatty acids was in good agreement with observed values of CH₄ production from the gas in vitro system. Dry matter intake per kilogram of body weight, organic matter digestibility and dietary concentrations of neutral detergent fibre, non-fibre carbohydrates and ether extract were the variables of the best fit model predicting CH₄ energy as a proportion of gross energy (prediction error 4.65% of the observed mean). The non-linear models developed proved to be more applicable over a wider range of intake for predicting total CH₄ production than linear models. Adjusting the exponents for dietary concentration of fat, proportion of non-fibre carbohydrates in total carbohydrates and organic matter digestibility improved the model. The sub-model predicting CH₄ production in the Karoline model was revised. Modifications were made to equations predicting digesta passage kinetics, microbial cell synthesis, digestion in the hind-gut and utilisation of hydrogen. The sensitivity analysis suggested that accurate values for digestion kinetic variables are required for accurate and acceptable predictions of CH₄ production with mechanistic models. The Karoline model was evaluated against published data (n=184 diets) reporting CH₄ production from in vivo trials. There was a good relationship between observed and predicted values of CH₄ production, with a small root mean square error of prediction (10.1% and 6.1% of the observed mean for fixed and mixed models, respectively). The mean bias was small (<2%) but statistically significant, and there was no slope bias. Most of the error was due to random bias (96.4%), whereas the contributions of mean and slope bias were small (3.4 and 0.2%, respectively).