gebhart/patrepeval huggingface dataset:
Infectious Diseases: Preparing for the Future (2006)

Epidemiological and modelling studies suggest that elimination of Onchocerca volvulus transmission (EoT) throughout Africa may not be achievable with annual mass drug administration (MDA) of ivermectin alone, particularly in areas of high endemicity and vector density.Single-dose Phase II and III clinical trials demonstrated moxidectin's superiority over ivermectin for prolonged clearance of O. volvulus microfilariae.We used the stochastic, individual-based EPIONCHO-IBM model to compare the probabilities of reaching EoT between ivermectin and moxidectin MDA for a range of endemicity levels (30 to 70% baseline microfilarial prevalence), treatment frequencies (annual and biannual) and therapeutic coverage/adherence values (65 and 80% of total population, with, respectively, 5 and 1% of systematic non-adherence).EPIONCHO-IBM's projections indicate that biannual (six-monthly) moxidectin MDA can reduce by half the number of years necessary to achieve EoT in mesoendemic areas and might be the only strategy that can achieve EoT in hyperendemic areas.Data needed to improve modelling projections include (i) the effect of repeated annual
Hypoxic Preconditioning Results in Increased Motility and Improved Therapeutic Potential of Human Mesenchymal Stem Cells (2008)

Mesenchymal stem cells (MSC) are adult multipotent cells found in bone marrow, adipose tissue, and other adult tissues. MSC have been shown to improve regeneration of injured tissues in vivo, but the mechanisms remain unclear. Typically, MSC are cultured under ambient, or normoxic, conditions (21% oxygen). However, the physiological niches for MSC in the bone marrow and other sites have much lower oxygen tension. When used as a therapeutic tool to repair tissue injuries, MSC cultured in standard conditions must adapt from 21% oxygen in culture to less than 1% oxygen in the ischemic tissue. We therefore examined the effects of preculturing human bone marrow-derived MSC in hypoxic conditions (1%-3% oxygen) to elucidate the best conditions that enhance their tissue regenerative potential. We demonstrated that MSC cultured in hypoxia activate the Akt signaling pathway while maintaining their viability and cell cycle rates. We also showed that MSC cultured in hypoxia induced expression of cMet, the major receptor for hepatocyte growth factor (HGF), and enhanced cMet signaling. MSC cultured in hypoxic conditions increased their migration rates. Since migration and HGF responsiveness are thought to be key mediators of MSC recruitment and/or activation in vivo, we next examined the tissue regenerative potential of MSC cultured under hypoxic conditions, using a murine hind limb ischemia model. We showed that local expression of HGF is increased in ischemic muscle in this model. Intra-arterial injection of MSC cultured in either normoxic or hypoxic conditions 24 hours after surgical induction of hind limb ischemia enhanced revascularization compared with saline controls. However, restoration of blood flow was observed significantly earlier in mice that had been injected with hypoxic preconditioned MSC. Collectively, these data suggest that preculturing MSC under hypoxic conditions prior to transplantation improves their tissue regenerative potential. Disclosure of potential conflicts of interest is found at the end of this article.
Precise targeted integration by a chimaeric transposase zinc-finger fusion protein (2009)

Transposons of the Tc1/mariner family have been used to integrate foreign DNA stably into the genome of a large variety of different cell types and organisms. Integration is at TA dinucleotides located essentially at random throughout the genome, potentially leading to insertional mutagenesis, inappropriate activation of nearby genes, or poor expression of the transgene. Here, we show that fusion of the zinc-finger DNA-binding domain of Zif268 to the C-terminus of ISY100 transposase leads to highly specific integration into TA dinucleotides positioned 6-17 bp to one side of a Zif268 binding site. We show that the specificity of targeting can be changed using Zif268 variants that bind to sequences from the HIV-1 promoter, and demonstrate a bacterial genetic screen that can be used to select for increased levels of targeted transposition. A TA dinucleotide flanked by two Zif268 binding sites was efficiently targeted by our transposase-Zif268 fusion, suggesting the possibility of designer 'Z-transposases' that could deliver transgenic cargoes to chosen genomic locations.
John Helsby Shergold 1938-2006 (2007)

Previous reports from treated psychiatric populations have reported a higher risk of mental illness among married females; however, community surveys often do not show this prevalence. Three referral groups, consisting of 488 subjects who were mentally ill but not seeking psychiatric treatment, provided a third type of population. For both sexes, combined drug and alcohol abusers were more likely to be divorced than to be married when compared to the rest of the study population (p less than .05). Both schizophrenia and drug and alcohol abuse showed differential findings by marital status and by sex, with the likelihood of more mentally ill females than males being married in these treatment populations.
Orexin/hypocretin signaling at the orexin 1 receptor regulates cue‐elicited cocaine‐seeking (2009)

The orexin/hypocretin system has recently been implicated in reward-processing and addiction. We examined the involvement of the orexin system in cue-induced reinstatement of extinguished cocaine-seeking by administering the orexin 1 receptor antagonist SB-334867 (SB) or the orexin 2 receptor antagonist 4-pyridylmethyl (S)-tert-leucyl 6,7-dimethoxy-1,2,3,4-tetrahydroisoquinoline (4PT) prior to reinstatement testing. Male Sprague Dawley rats self-administered cocaine in 2-h sessions for 10 days, followed by extinction training. Reinstatement of cocaine-seeking was elicited by presentation of tone + light cues previously paired with cocaine infusions. SB (10, 20 and 30 mg/kg) dose-dependently decreased cue-induced reinstatement of cocaine-seeking without significantly affecting responding during late extinction. 4PT (10 and 30 mg/kg) did not significantly alter cue-induced reinstatement. In separate experiments, the highest doses of SB and 4PT had no significant effect on established cocaine self-administration, and 4PT reduced spontaneous activity in a locomotor test to a greater extent than SB. Finally, SB (30 mg/kg) had no effect on the acquisition of cocaine-paired cues during a Pavlovian cocaine-stimulus conditioning session in the operant chamber. Pretreatment with SB prior to the Pavlovian acquisition session had no effect on subsequent cue-induced reinstatement of cocaine-seeking elicited by those cues. However, pretreatment with SB prior to a second reinstatement session in the same animals significantly attenuated the expression of cue-induced reinstatement. These results show that orexin transmission at the orexin 1 receptor, but not the orexin 2 receptor, is necessary for the reinstatement of cocaine-seeking elicited by drug-paired cues and that orexin signaling is not critical for cocaine reinforcement or cocaine-stimulus conditioning.
1877: DEXMEDETOMIDINE FOR TREATMENT OF REFRACTORY OPIOID WITHDRAWAL (2016)

Copyright © 2016 by the Society of Critical Care Medicine and Wolters Kluwer Health, Inc. All Rights Reserved.
Reduction of infarct size with intracoronary perfluorochemical in a canine preparation of reperfusion. (1985)

The effect of low-dose (15 ml/kg) intracoronary perfluorochemical (Fluosol-DA) on infarct size, regional myocardial blood flow, and ventricular function was studied in 20 anesthetized closed-chest dogs subjected to 11/2 hr of proximal left anterior descending occlusion. In this preparation reperfusion was simulated with fibrinolytic therapy. The animals were randomly assigned one of two treatment groups and given 15 ml/kg of either oxygenated intracoronary perfluorochemical (n = 9) or saline (n = 11). Contrast ventriculograms were obtained at baseline, 1 hr after occlusion, and at 24 hr after reperfusion and were analyzed with a radial fractional shortening method. Regional myocardial blood flow was measured with radioactive microspheres. At 24 hr the area at risk was defined in vivo with monastryl blue staining and the area of necrosis was estimated after incubation of left ventricular slices with triphenyltetrazolium chloride. No significant changes were noted in heart rate, blood pressure, pulmonary capillary wedge pressure, or dP/dt during the experimental protocol. Infarct size was significantly reduced (p less than .02) in the perfluorochemical-treated group, both when expressed as a percentage of the total left ventricular mass (7.9 +/- 1.7% vs 14.7 +/- 2.5%) and as a percentage of the area at risk (20.1 +/- 5.0% vs 46.8 +/- 8.5%). This was associated with significant improvement in fractional shortening in the jeopardized zone at 24 hr after reperfusion. Although endocardial blood flow was significantly greater in the central ischemic zone and lateral region at risk immediately after reperfusion in the perfluorochemical-treated group, no difference was found 1 hr after reperfusion.(ABSTRACT TRUNCATED AT 250 WORDS)
Design superiority of palindromic DNA sites for site-specific recognition of proteins: tests using protein stitchery. (1993)

Using protein stitchery with appropriate attachment of cysteines linking to either C or N termini of the basic region of the v-Jun leucine zipper gene-regulatory protein, we constructed three dimers--pCC, pCN, and pNN. All three bind specifically to the appropriately rearranged DNA recognition sites for v-Jun: ATGAcgTCAT, ATGAcgATGA, and TCATcgTCAT, respectively (Kd, approximately 4 nM at 4 degrees C). Results of DNase I footprinting provide strong support for bent recognition helices in leucine zipper protein-DNA complexes. Comparison of the results for pCC and pNN with those for pCN shows the design superiority of palindromic sequences for protein recognition.
What Makes Transcutaneous Electrical Nerve Stimulation Work? Making Sense of the Mixed Results in the Clinical Literature (2013)

Transcutaneous electrical nerve stimulation (TENS) is a nonpharmacological treatment for control of pain. It has come under much scrutiny lately with the Center for Medicare Services rendering a recent decision stating that "TENS is not reasonable and necessary for the treatment of CLBP [chronic low back pain]." When reading and analyzing the existing literature for which systematic reviews show that TENS is inconclusive or ineffective, it is clear that a number of variables related to TENS application have not been considered. Although many of the trials were designed with the highest of standards, recent evidence suggests that factors related to TENS application need to be considered in an assessment of efficacy. These factors include dosing of TENS, negative interactions with long-term opioid use, the population and outcome assessed, timing of outcome measurement, and comparison groups. The purpose of this perspective is to highlight and interpret recent evidence to help improve the design of clinical trials and the efficacy of TENS in the clinical setting.
Nine-Hospital Study Comparing Broth Microdilution and Etest Method Results for Vancomycin and Daptomycin against Methicillin-Resistant Staphylococcus aureus (2009)

Vancomycin and daptomycin MIC results for 1,800 randomly selected oxacillin (methicillin [meticillin])-resistant Staphylococcus aureus (MRSA) bloodstream isolates from nine U.S. hospitals (collected from 2002 to 2006) were determined by a reference broth microdilution (BMD) method using frozen-form panels with precise incremental dilutions and by the Etest technique. The Etest provided vancomycin and daptomycin MIC results that were consistently higher (0.5 to 1.5 log(2) dilution steps) than those provided by the reference BMD method. The dominant MRSA population (91.2% of MRSA isolates) would be categorized as vancomycin nonsusceptible by the MIC results from the Etest method if the susceptibility breakpoint was adjusted downward to < or =1 microg/ml, as suggested by clinical outcome studies.
Specific expression of a retinoic acid-regulated, zinc-finger gene, Rex-1, in preimplantation embryos, trophoblast and spermatocytes (1991)

We have previously isolated a cDNA clone for a gene whose expression is reduced by retinoic acid (RA) treatment of F9 embryonal carcinoma cells. The nucleotide sequence indicated that this gene, Rex-1, encodes a zinc-finger protein and thus may be a transcriptional regulator. The Rex-1 message level is high in two lines of embryonic stem cells (CCE and D3) and is reduced when D3 cells are induced to differentiate using four different growth conditions. As expected for a stem-cell-specific message, Rex-1 mRNA is present in the inner cell mass (ICM) of the day 4.5 mouse blastocyst. It is also present in the polar trophoblast of the blastocyst. One and two days later, Rex-1 message is found in the ectoplacental cone and extraembryonic ectoderm of the egg cylinder (trophoblast-derived tissues), but its abundance is much reduced in the embryonic ectoderm which is directly descended from the ICM. Rex-1 is expressed in the day 18 placenta (murine gestation is 18 days), a tissue which is largely derived from trophoblast. The only tested adult tissue that contains detectable amounts of Rex-1 mRNA is the testis. In situ hybridization and northern analyses of RNA from germ-cell-deficient mouse testis and stage-specific germ cell preparations suggest that Rex-1 expression is limited to spermatocytes (germ cells undergoing meiosis). These results suggest that Rex-1 is involved in trophoblast development and spermatogenesis, and is a useful marker for studies of early cell fate determination in the ICM.
Powering a Ventricular Assist Device (VAD) With the Free-Range Resonant Electrical Energy Delivery (FREE-D) System (2011)

Wireless data communication technology has eliminated wired connections for data transfer to portable devices. Wireless power technology offers the possibility of eliminating the remaining wired connection: the power cord. For ventricular assist devices (VADs), wireless power technology will eliminate the complications and infections caused by the percutaneous wired power connection. Integrating wireless power technology into VADs will enable VAD implants to become a more viable option for heart failure patients (of which there are 80 000 in the United States each year) than heart transplants. Previous transcutaneous energy transfer systems (TETS) have attempted to wirelessly power VADs ; however, TETS-based technologies are limited in range to a few millimeters, do not tolerate angular misalignment, and suffer from poor efficiency. The free-range resonant electrical delivery (FREE-D) wireless power system aims to use magnetically coupled resonators to efficiently transfer power across a distance to a VAD implanted in the human body, and to provide robustness to geometric changes. Multiple resonator configurations are implemented to improve the range and efficiency of wireless power transmission to both a commercially available axial pump and a VentrAssist centrifugal pump [3]. An adaptive frequency tuning method allows for maximum power transfer efficiency for nearly any angular orientation over a range of separation distances. Additionally, laboratory results show the continuous operation of both pumps using the FREE-D system with a wireless power transfer efficiency upwards of 90%.
Circulating Tumor Cell as a Diagnostic Marker in Primary Lung Cancer (2009)

CTC is a useful surrogate marker of distant metastasis in primary lung cancer.
Screening and Surveillance for the Early Detection of Colorectal Cancer and Adenomatous Polyps, 2008: A Joint Guideline from the American Cancer Society, the US Multi-Society Task Force on Colorectal Cancer, and the American College of Radiology (2008)

In the United States, colorectal cancer (CRC) is the third most common cancer diagnosed among men and women and the second leading cause of death from cancer. CRC largely can be prevented by the detection and removal of adenomatous polyps, and survival is significantly better when CRC is diagnosed while still localized. In 2006 to 2007, the American Cancer Society, the US Multi Society Task Force on Colorectal Cancer, and the American College of Radiology came together to develop consensus guidelines for the detection of adenomatous polyps and CRC in asymptomatic average-risk adults. In this update of each organization's guidelines, screening tests are grouped into those that primarily detect cancer early and those that can detect cancer early and also can detect adenomatous polyps, thus providing a greater potential for prevention through polypectomy. When possible, clinicians should make patients aware of the full range of screening options, but at a minimum they should be prepared to offer patients a choice between a screening test that is effective at both early cancer detection and cancer prevention through the detection and removal of polyps and a screening test that primarily is effective at early cancer detection. It is the strong opinion of these 3 organizations that colon cancer prevention should be the primary goal of screening.
Lines of Murine Oligodendroglial Precursor Cells Immortalized by an Activated neu Tyrosine Kinase Show Distinct Degrees of Interaction with Axons In Vitro and In Vivo (1995)

Replication-defective retroviruses expressing the t-neu oncogene, or a hybrid protein with the neu tyrosine kinase linked to the external region of the human epidermal growth factor receptor (egfr-neu), were used to establish lines of murine oligodendroglial precursor cells. Differentiation of the t-neu lines into myelin-associated glycoprotein (MAG)-positive oligodendrocytes was induced by dibutyryl cAMP, and the egfr-neu line showed limited differentiation in vitro upon withdrawal of epidermal growth factor. Cerebellar granule cell neurons expressed mitogens for the cell lines. Upon transplantation into demyelinated lesions, t-neu line cells engaged with the demyelinated axons whereas the egfr-neu line cells differentiated further and ensheathed the axons. These cell lines thus interact with neurons in vitro and in vivo and can be used as tools to define the molecules involved in different stages of neuron-glia interaction.
The Forkhead Transcription Factor Foxo1 Bridges the JNK Pathway and the Transcription Factor PDX-1 through Its Intracellular Translocation (2005)

It has been shown that oxidative stress and activation of the c-Jun N-terminal kinase (JNK) pathway induce the nucleocytoplasmic translocation of the pancreatic transcription factor PDX-1, which leads to pancreatic beta-cell dysfunction. In this study, we have shown that the forkhead transcription factor Foxo1/FKHR plays a role as a mediator between the JNK pathway and PDX-1. Under oxidative stress conditions, Foxo1 changed its intracellular localization from the cytoplasm to the nucleus in the pancreatic beta-cell line HIT-T15. The overexpression of JNK also induced the nuclear localization of Foxo1, but in contrast, suppression of JNK reduced the oxidative stress-induced nuclear localization of Foxo1, suggesting the involvement of the JNK pathway in Foxo1 translocation. In addition, oxidative stress or activation of the JNK pathway decreased the activity of Akt in HIT cells, leading to the decreased phosphorylation of Foxo1 following nuclear localization. Furthermore, adenovirus-mediated Foxo1 overexpression reduced the nuclear expression of PDX-1, whereas repression of Foxo1 by Foxo1-specific small interfering RNA retained the nuclear expression of PDX-1 under oxidative stress conditions. Taken together, Foxo1 is involved in the nucleocytoplasmic translocation of PDX-1 by oxidative stress and the JNK pathway.
The Existence of Multiple Conformers of Interleukin-21 Directs Engineering of a Superpotent Analogue (2007)

The high resolution three-dimensional structure of human interleukin (hIL)-21 has been resolved by heteronuclear NMR spectroscopy. Overall, the hIL-21 structure is dominated by a well defined central four-helical bundle, arranged in an up-up-down-down topology, as observed for other cytokines. A segment of the hIL-21 molecule that includes the third helical segment, helix C, is observed to exist in two distinct and interchangeable states. In one conformer, the helix C segment is presented in a regular, alpha-helical conformation, whereas in the other conformer, this segment is largely disordered. A structure-based sequence alignment of hIL-21 with receptor complexes of the related cytokines, interleukin-2 and -4, implied that this particular segment is involved in receptor binding. An hIL-21 analog was designed to stabilize the region around helix C through the introduction of a segment grafted from hIL-4. This novel hIL-21 analog was demonstrated to exhibit a 10-fold increase in potency in a cellular assay.
SYNTHESIS OF 3-SUBSTITUTED 1,4-BENZODIAZEPINE-2-ONES (1978)

(1978). SYNTHESIS OF 3-SUBSTITUTED 1,4-BENZODIAZEPINE-2-ONES. Organic Preparations and Procedures International: Vol. 10, No. 3, pp. 105-111.
Fabrication of NiAl intermetallic reactors for microtechnology-based energy chemical systems (MECS) (2001)

Exogenous cathelicidin modulates C difficile colitis by inhibiting TxA-associated intestinal inflammation. Cathelicidin administration may be a new anti-inflammatory treatment for C difficile toxin-associated disease.
Iron regulation by hepcidin (2013)

Hepcidin is a key hormone that is involved in the control of iron homeostasis in the body. Physiologically, hepcidin is controlled by iron stores, inflammation, hypoxia, and erythropoiesis. The regulation of hepcidin expression by iron is a complex process that requires the coordination of multiple proteins, including hemojuvelin, bone morphogenetic protein 6 (BMP6), hereditary hemochromatosis protein, transferrin receptor 2, matriptase-2, neogenin, BMP receptors, and transferrin. Misregulation of hepcidin is found in many disease states, such as the anemia of chronic disease, iron refractory iron deficiency anemia, cancer, hereditary hemochromatosis, and ineffective erythropoiesis, such as β-thalassemia. Thus, the regulation of hepcidin is the subject of interest for the amelioration of the detrimental effects of either iron deficiency or overload.
Papillary thyroid carcinoma with massive metastasis in the uterine corpus: a case report (2013)

In this report, an unusual case of PTC was presented. The patient had not only regional lymphatic metastasis, but also had a massive metastasis in the uterine corpus, which was initially misdiagnosed as ovarian carcinoma. This case is of interest because of its rarity and exceptionally good prognosis. The reason for the misdiagnosis was attributed to overlooking the possibility of a distant metastasis coming from a PTC. This case raises the issue that completing an iodine-131 scan before operating on patients with PTC may be warranted.