gebhart/patrepeval huggingface dataset:
Actual treatment of overactive bladder and urge urinary incontinence. (2013)

Overactive bladder (OAB) is defined by its hallmark symptom, urgency. It can be associated with urge urinary incontinence (UUI), and dramatically impact the patients' quality of life. Etiologies of OAB are numerous, and under this common wording, virtually all the population is covered (men as well as women, patients with or without neurogenic disease, and all age categories). OAB and UUI management have been historically based on non-interventional therapies, antimuscarinics, and surgery. In the last decade, innovations in the treatment of this highly prevalent condition have been multiple, and further insights came from various horizons (drug invention, innovative use of existing drugs, new medical devices, tissue engineering, gene and cell therapy). Notably, the use of BoNT and neuromodulation techniques have deeply modified the algorithm of specialized OAB management, delaying surgery indications and offering mini-invasive alternatives to patient refractory to behavioral and medical treatment. Whilst some of these techniques are about to reach maturity, numerous questions remain unsolved about their indications, long term effects, rank in the armamentarium, cost-effectiveness, hypothetical combination or sequential use. The present review depicts the actual wide range of options available for OAB management in adults, focusing on the latest evolutions. When relevant, a distinction was made between genders and OAB subtypes (idiopathic vs neurogenic) regarding treatment outcomes.
C1q Protein Binds to the Apoptotic Nucleolus and Causes C1 Protease Degradation of Nucleolar Proteins (2015)

In infection, complement C1q recognizes pathogen-congregated antibodies and elicits complement activation. Among endogenous ligands, C1q binds to DNA and apoptotic cells, but whether C1q binds to nuclear DNA in apoptotic cells remains to be investigated. With UV irradiation-induced apoptosis, C1q initially bound to peripheral cellular regions in early apoptotic cells. By 6 h, binding concentrated in the nuclei to the nucleolus but not the chromatins. When nucleoli were isolated from non-apoptotic cells, C1q also bound to these structures. In vivo, C1q exists as the C1 complex (C1qC1r2C1s2), and C1q binding to ligands activates the C1r/C1s proteases. Incubation of nucleoli with C1 caused degradation of the nucleolar proteins nucleolin and nucleophosmin 1. This was inhibited by the C1 inhibitor. The nucleoli are abundant with autoantigens. C1q binding and C1r/C1s degradation of nucleolar antigens during cell apoptosis potentially reduces autoimmunity. These findings help us to understand why genetic C1q and C1r/C1s deficiencies cause systemic lupus erythematosus.
Cell Adhesion as Wetting Transition? (2002)

Cell adhesion is controlled by a complex interplay of short range (lock-and-key) forces mediated by cell surface receptors, a phalanx of (short and long range) nonspecific (generic) interactions, and last but not least membrane elasticity. The physical basis of cell adhesion is explored by the design of simplified model systems, mimicking cell and tissue surfaces, enabling local measurements of cellular shape changes and adhesion forces by microinterferometry. Cell adhesion can be understood as first-order dewetting transition that results in the formation of adhesion plaques, such as focal adhesion sites of cells, which allow cell adhesion at astonishingly low receptor densities. The repeller molecules of the glycocalix play a key role for the control of the adhesion transition and the mechanical stability of the adhering cells by relaxing the strength of the binding forces. Stress fibers are postulated to be essential for the stabilization of adhesion domains against leverage through bending moments enforced by hydrodynamic shear forces.
The tumorigenicity of diploid and aneuploid human pluripotent stem cells (2009)

Human embryonic stem cells (HESCs) and induced pluripotent stem cells (HiPSCs) offer an immense potential as a source of cells for regenerative medicine. However, the ability of undifferentiated HESCs and HiPSCs to produce tumors in vivo presents a major obstacle for the translation of this potential into clinical reality. Therefore, characterizing the nature of HESC- and HiPSC-derived tumors, especially their malignant potential, is extremely important in order to evaluate the risk involved in their clinical use. Here we review recent observations on the tumorigenicity of human pluripotent stem cells. We argue that diploid, early passage, HESCs produce benign teratomas without undergoing genetic modifications. Conversely, HESCs that acquired genetic or epigenetic changes upon adaptation to in vitro culture can produce malignant teratocarcinomas. We discuss the molecular mechanisms of HESC tumorigenicity and suggest approaches to prevent tumor formation from these cells. We also discuss the differences in the tumorigenicity between mouse embryonic stem cells (MESCs) and HESCs, and suggest methodologies that may help to identify cellular markers for culture adapted HESCs.
Probiotic Escherichia coli strain Nissle 1917 outcompetes intestinalpathogens during biofilm formation (2010)

Many bacterial infections are associated with biofilm formation. Bacterial biofilms can develop on essentially all kinds of surfaces, producing chronic and often intractable infections. Escherichia coli is an important pathogen causing a wide range of gastrointestinal infections. E. coli strain Nissle 1917 has been used for many decades as a probiotic against a variety of intestinal disorders and is probably the best field-tested E. coli strain in the world. Here we have investigated the biofilm-forming capacity of Nissle 1917. We found that the strain was a good biofilm former. Not only was it significantly better at biofilm formation than enteropathogenic, enterotoxigenic and enterohaemorrhagic E. coli strains, it was also able to outcompete such strains during biofilm formation. The results support the notion of bacterial prophylaxis employing Nissle 1917 and may partially explain why the strain has a beneficial effect on many intestinal disorders.
Immunogenicity of human amniotic membrane in experimental xenotransplantation. (2001)

Amniotic membrane seems to be immune-privileged tissue and to contain some immunoregulatory factors, including HLA-G and Fas ligand. The amniotic membrane may be useful to supplement corneal collagen, and it may be applied not only to the ocular surface but also intracorneally.
Engineering batch and pulse refolding with transition of aggregation kinetics: An investigation using green fluorescent protein (GFP) (2015)

Pulse refolding is a strategy to overcome concentration dependent aggregation, assuming that aggregation is significantly suppressed under diluted conditions. When a typical 2nd or higher order aggregation kinetics is assumed, kinetics over predicted yields at low refolding concentrations. Using GFP as our model protein, we found a transition in aggregation kinetics from 2nd to 1st order when intermediates deplete from 100 to 60 µg/ml. Taking this transition into account, the model can better predict refolding yields in batch and pulse refolding strategies. This model is suited for the design of refolding processes since this deviation from 2nd or higher order aggregation was also previously observed in other proteins.
Scheduling disciplines for HFC systems: what can we learn from ATM scheduling? (2002)

The support of multimedia traffic with different quality of service (QoS) requirements on an integrated network has proven to be difficult. It requires simple design of conceptually complex mechanisms. We study the application of proposed ATM scheduling disciplines to a hybrid fiber/coaxial (HFC) system. Switching networks are based on point-to-point communication links whereas HFC is a shared medium. If we can show that the structural differences between the environments do not affect the functionality of the scheduler a great amount of knowledge on supporting QoS can be imported to HFC systems from switching studies. As an example self clock fair queueing (SCFQ) is embedded in an HFC system. Simulation results show that the scheduler maintains its capabilities in guaranteeing the QoS in the HFC system.
Prodrugs of nitroxyl as inhibitors of aldehyde dehydrogenase (1992)

In the preceding paper, analogs of chlorpropamide with an OMe substituent on the sulfonamide nitrogen were shown to inhibit aldehyde dehydrogenase (AlDH), and it was postulated that these compounds were bioactivated by O-demethylation to release nitroxyl (HN = O, nitrosyl hydride), which is an inhibitor of AlDH. Further evidence for the production of nitroxyl from compounds with O-acyl instead of OMe on the sulfonamide nitrogen is now presented. Thus, nitrous oxide (N2O), the end product of nitroxyl dimerization and disproportionation, was found to be generated on alkaline or enzymatic hydrolysis of N,O-diacylated N-hydroxyarylsulfonamides. Since the latter compounds strongly inhibit yeast AlDH in vitro after bioactivation by an esterase intrinsic to this enzyme, nitroxyl generated from these compounds must be the common intermediate that inhibits AlDH.
Adiponectin in Fresh Frozen Plasma Contributes to Restoration of Vascular Barrier Function After Hemorrhagic Shock (2015)

Hemorrhagic shock is the leading cause of preventable deaths in civilian and military trauma. Use of fresh frozen plasma (FFP) in patients requiring massive transfusion is associated with improved outcomes. FFP contains significant amounts of adiponectin, which is known to have vascular protective function. We hypothesize that FFP improves vascular barrier function largely via adiponectin. Plasma adiponectin levels were measured in 19 severely injured patients in hemorrhagic shock (HS). Compared with normal individuals, plasma adiponectin levels decreased to 49% in HS patients before resuscitation (P < 0.05) and increased to 64% post-resuscitation (but not significant). In a HS mouse model, we demonstrated a similar decrease in plasma adiponectin to 54% but a significant increase to 79% by FFP resuscitation compared with baseline (P < 0.05). HS disrupted lung vascular barrier function, leading to an increase in permeability. FFP resuscitation reversed these HS-induced effects. Immunodepletion of adiponectin from FFP abolished FFP's effects on blocking endothelial hyperpermeability in vitro, and on improving lung vascular barrier function in HS mice. Replenishment with adiponectin rescued FFP's effects. These findings suggest that adiponectin is an important component in FFP resuscitation contributing to the beneficial effects on vascular barrier function after HS.
FimH Antagonists: Phosphate Prodrugs Improve Oral Bioavailability (2016)

The widespread occurrence of urinary tract infections has resulted in frequent antibiotic treatment, contributing to the emergence of antimicrobial resistance. Alternative approaches are therefore required. In the initial step of colonization, FimH, a lectin located at the tip of bacterial type 1 pili, interacts with mannosylated glycoproteins on the urothelial mucosa. This initial pathogen/host interaction is efficiently antagonized by biaryl α-d-mannopyranosides. However, their poor physicochemical properties, primarily resulting from low aqueous solubility, limit their suitability as oral treatment option. Herein, we report the syntheses and pharmacokinetic evaluation of phosphate prodrugs, which show an improved aqueous solubility of up to 140-fold. In a Caco-2 cell model, supersaturated solutions of the active principle were generated through hydrolysis of the phosphate esters by brush border-associated enzymes, leading to a high concentration gradient across the cell monolayer. As a result, the in vivo application of phosphate prodrugs led to a substantially increased Cmax and prolonged availability of FimH antagonists in urine.
A 31-dBm, high ruggedness power amplifier in 65-nm standard CMOS with high-efficiency stacked-cascode stages (2010)

A novel, high ruggedness power amplifier topology in a 65-nm CMOS technology is proposed. The proposed stacked cascode topology uses only standard devices available in a modern triple-well CMOS process to achieve breakdown voltages of more than 18V. The power amplifier stage delivers 28 dBm output power at a power-added efficiency (PAE) of 69.9% from a 3.6V supply. The saturation gain is 18 dB. A watt-level power amplifier for GSM low-band operation with 31-dBm output power and 61% PAE is presented.
National Science Foundation-Sponsored Workshop Report. Draft Plan for Soybean Genomics (2004)

Recent efforts to coordinate and define a research strategy for soybean (Glycine max) genomics began with the establishment of a Soybean Genetics Executive Committee, which will serve as a communication focal point between the soybean research community and granting agencies. Secondly, a workshop was held to define a strategy to incorporate existing tools into a framework for advancing soybean genomics research. This workshop identified and ranked research priorities essential to making more informed decisions as to how to proceed with large scale sequencing and other genomics efforts. Most critical among these was the need to finalize a physical map and to obtain a better understanding of genome microstructure. Addressing these research needs will require pilot work on new technologies to demonstrate an ability to discriminate between recently duplicated regions in the soybean genome and pilot projects to analyze an adequate amount of random genome sequence to identify and catalog common repeats. The development of additional markers, reverse genetics tools, and bioinformatics is also necessary. Successful implementation of these goals will require close coordination among various working groups.
Role of Urine Toxicology Testing in the Management of Chronic Opioid Therapy (2002)

Recognition is growing that self-report of drug use, prescribed or otherwise, among patients with chronic pain treated with opioids is often unreliable. This fact is well known to the addiction management community. Patients may inaccurately report use of prescribed medications, fail to report use of nonprescribed medications or medications prescribed by other physicians, or fail to report use of illicit drugs. Although there are yet no accepted diagnostic criteria for addiction or other forms of medication misuse in the patient with chronic pain, most clinicians would agree that awareness of a patient's inappropriate use of nonprescribed medications or illicit drugs is relevant to proper patient management. The use of external sources of information, therefore, such as testing of biologic material (e.g., urine), interviews with spouses, review of medical records, or input from prescription monitoring programs, may improve patient management. Of these methods, urine toxicology testing has by far the largest experience. Urine toxicology testing may reveal the presence of illicit drugs, such as heroin or cocaine, or controlled substances not prescribed by the physician ordering the test (e.g., hydromorphone in a patient prescribed oxycodone). The authors review the use of urine toxicology testing in monitoring patients with chronic pain, including laboratory aspects. They also present evidence from recent studies that suggests that monitoring the behavior alone of patients on chronic opioid treatment will fail to detect potential problems revealed by urine toxicology testing. The authors conclude that, although further research is urgently needed, at this time it is appropriate to conduct routine urine toxicology testing in patients with chronic pain treated with opioids.
Influence of Tumor pH on Therapeutic Response (2007)

The intratumor microenvironment is intrinsically acidic due mainly to accumulation of lactic acid as a result of increased aerobic and anaerobic glycolysis by the tumor cells. In general, the extracellular pH (pHe) in human tumors is below 7.0, whereas the intracellular pH (pHi) is maintained at neutral range, i.e.,>7.0, by powerful pHi control mechanisms. The low pHe and the significant gradients between pHe and pHi affect markedly the response of tumors to various treatments such as chemotherapy, radiotherapy and hyperthermia. For instance, the acidic pHe increases the cellular uptake of weakly acidic drugs such as cyclophosphamide and cisplatin and thus increases the effect of the drugs, whereas the acidic pHe retards the uptake of weakly basic drug such as doxorubicin and vinblastine, thereby reducing the effect of the drugs. The radiationinduced apoptosis is suppressed by an acidic environment, whereas the hyperthermiainduced cell death is potentiated by an acidic environment. Better understanding of the control mechanisms of pHe and pHi in tumors may lead to device effective treatment strategy of human tumors.
A Battery-Powered Notebook Thermal Cycler for Rapid Multiplex Real-Time PCR Analysis (2000)

A compact, real-time PCR instrument was developed for rapid, multiplex analysis of nucleic acids in an inexpensive, portable format. The instrument consists of a notebook computer, two reaction modules with integrated optics for four-color fluorescence detection, batteries, and a battery-charging system. The instrument weighs 3.3 kg, measures 26 x 22 x 7.5 cm, and can run continuously on the internal batteries for 4 h. Independent control of the modules allows differing temperature profiles and detection schemes to be run simultaneously. Results are presented that demonstrate rapid (1) detection and identification of Bacillus subtilis and Bacillus thuringensis spores and (2) characterization of a single nucleotide polymorphism for the hereditary hemochromatosis gene.
Origin of rat beta-globin haplotypes containing three and five genes. (1990)

We have reported in rat three adult beta-gene haplotypes containing either five or three genes. Detailed sequence analysis reveals that the leftmost gene is the major gene and that at the opposite end downstream lies the minor gene. All of the genes lying between them are minor-major hybrids indicating their origin by unequal crossing-over. In two haplotypes beta-globin genes were found with an L1(1) element inserted directly into IVS2. The described results allow the formulation of a pathway of mutational events leading from the ancient two-beta-gene rodent ancestor through a three-gene haplotype to five-gene haplotypes, one of which is postulated to have arisen in common laboratory strains since their capture in the wild.
Complications after Selective Posterior Rhizotomy for Spasticity in Children with Cerebral Palsy (1998)

Selective dorsal rhizotomy (SDR) has been shown to be an effective treatment for the spasticity of cerebral palsy, but few studies have addressed specifically the side effects of the procedure. A retrospective study was performed to determine the frequency and nature of complications in 158 children who had undergone SDR at British Columbia's Children's Hospital from 1987 to 1996. Intraoperative, preoperative (immediate postoperative until discharge at approximately 7 days) and postdischarge complications occurred in 3.8, 43.6 and 30% of patients, respectively. The most common intraoperative complication was aspiration pneumonia, which was experienced by 2 patients (1.3%). Perioperatively, sensory changes were found in 8.9% of the children, and transient urinary retention in 4.4%. Complications after discharge included back pain starting more than 6 months after surgery in 10.8%, sensory changes in 13.9%, and neurogenic bladder or bowel problems in 12.7%. Persistent sensory changes occurred in 3.8%, were not important functionally, and tended to occur in patients with the largest amount of dorsal root tissue cut. In 8 patients (5.1%), bladder and/or bowel dysfunction attributed to the SDR was present at the latest follow-up, although in only 2 patients (1.3%) this dysfunction was a definite complication of the rhizotomy. The use of pudendal monitoring and/or cutting less than 50% of the S2 roots may have been associated with a lower incidence of long-term sphincter dysfunction. Data about the nature and frequency of complications may result in further modifications to the SDR procedure, and is critical for counseling about SDR and alternative options available for treatment of the child with spastic cerebral palsy.
Clinical Pharmacokinetics of Daptomycin (1990)

Daptomycin is a new lipopeptide antibiotic for which preliminary pharmacokinetic data in adults have been limited to normal healthy volunteers and patients with renal insufficiency. We report the clinical pharmacokinetics of the first and fifth doses of iv daptomycin 150 mg (2 mg/kg) q24h in a 29-year-old man being treated for a gram-positive cellulitis and thrombophlebitis. Individual pharmacokinetic parameters yielded similar results during doses one and five. The pharmacokinetic profile observed in our patient did not markedly differ from data obtained from healthy volunteers.
Heparin Inhibits the Immediate Response to Antigen in the Skin and Lungs of Allergic Subjects (1993)

Although heparin is used as an anticoagulant, its biologic function remains unclear. Substantial evidence exists that suggests it may modulate many aspects of immune function and inflammation. We demonstrated, in a double-blind, placebo-controlled, crossover study involving 10 allergic subjects, that a small dose of heparin (25 U/kg) administered intravenously 10 min before challenge reduced the acute cutaneous reaction to 10 allergens and histamine from a group-average sum of mean (+/- SD) wheal diameters at a baseline of 29.9 +/- 10 mm and after normal saline placebo (29.5 +/- 10.7 mm) to after heparin (14.4 +/- 10.4 mm) (p < 0.02, Wilcoxon's signed rank test). In 15 subjects with asthma and dust mite allergy, nebulized heparin 20,000 units administered in a double-blind, placebo-controlled, crossover fashion 10 min before challenge inhibited the bronchospasm induced by inhaled dust mite extract. Log2 of the provocative dose of mite extract causing a 20% fall in FEV1 at baseline was 4.1 +/- 1.5 protein nitrogen units (PNU); after normal saline it was 4.5 +/- 2.0 PNU, and after heparin it was 5.1 +/- 2.5 PNU (p = 0.04). These data suggest heparin may have an inhibitory role in acute mast-cell-mediated allergic inflammation.
National support for NPs. (2012)

Recent data published by the Nursing and Midwifery Board of Australia (NMBA) in August 2012 shows there are now 7361 endorsed Nurse Practitioners (NPs) in Australia. NSW are leading the way in growing NP numbers, with Queensland a super close second.
Proteolytically modified human beta2-microglobulin augments the specific cytotoxic activity in murine mixed lymphocyte culture. (1987)

A proteolytically modified form of beta 2-microglobulin (beta 2-m) present in the serum of patients suffering from autoimmune, immunodeficient diseases and cancer has been reported in the literature. In the present study we show that human beta 2-m as well as the proteolytically modified human form (M-beta 2-m) bind to murine lymphocytes expressing H-2 class I antigens; M-beta 2-m, when added at day 0 and 1 of culture in nanomolar concentrations to a one-way murine allogeneic mixed lymphocyte culture (MLC) augments the generation of specific cytotoxic T lymphocytes; M-beta 2-m increases the endogenous production of interleukin 2 in the MLC culture; monoclonal antibody which reacts with both the native beta 2-m and M-beta 2-m molecule blocks the augmentation of cytotoxic T lymphocyte production induced by M-beta 2-m; murine as well as human MLC responder cells can proteolytically modify native human beta 2-m; and the modifying activity of murine MLC responder cells was blocked in an intermediary step by an alloantibody, which reacts specifically with murine major histocompatibility complex, class I-associated beta 2-m. These findings suggest that the modification process is preceded by an association of human beta 2-m with the cell surface of the responder cells. Our data indicate that the modification of beta 2-m might reflect early events in allospecific responder cell activation.