Miracle-dz/UniFAR-FTUs huggingface dataset:
Itx 5061 Quantitation in Human Plasma with Reverse Phase Liquid Chromatography and Mass Spectrometry Detection

Background ITX 5061 is a highly potent small molecule inhibitor of scavenger receptor-B1, an integral transmembrane protein that is found in liver cells and is actively involved in the transport of HCV into hepatocytes. Currently, ITX 5061 is being investigated in monoinfected hepatitis C patients in a proof-of-concept clinical trial carried out by the AIDS Clinical Trial Group (ACTG). Methods To provide quantitative results in human plasma for pharmacokinetic analysis, an assay for ITX 5061 was validated. ITX 5061 and the internal standard, a deuterated analogue, were separated by isocratic reverse phase chromatography using a Polar RP column (Phenomenex Synergi™; 2.0 mmx50 mm, 4 μm) and detected via electrospray coupled to a triple quadrupole mass spectrometer with a run time of 5 min. Multiple reaction monitoring in positive mode was used with ITX 5061 at 585/114 m/z and the internal standard at 592/122 m/z with a linear range of 2.50–5,000 ng/ml. Human plasma was extracted using a protein precipitation combing 400 μl of acetonitrile with 100 μl of EDTA plasma. Results The interassay variation ranged from 1.19 to 13.2%, while the intraassay variation ranged from 0.394 to 12.9% over 6 days of testing. The method was successfully applied to the samples collected for the ACTG Protocol A5277. Plasma concentrations at 1 h and 24 h following 150 mg ITX 5061 daily in HCV monoinfected patients (n=3) ranged from 138 to 518 ng/ml and 33 to 111 ng/ml, respectively. Conclusions The ITX 5061 assay is accurate and reproducible with a wide linear range and will be used for pharmacokinetic analysis and dose-finding studies in HCV-monoinfected patients.
Patterns and persistence of behavioural and psychological symptoms in those with cognitive impairment: the importance of apathy

To study the stability and emergence of a range of behavioural and psychological symptoms (BPS), their association with mortality and the effect of covariates on these transitions in a population‐based study of cognitively impaired older people with a long follow‐up period and large sample size, with a particular focus on apathy.
Preischemic and postischemic treatment with a new Na+/H+-exchange inhibitor, FR183998, shows cardioprotective effects in rats with cardiac ischemia and reperfusion.

This study describes the pharmacologic profile of a new Na+/H(+)-exchange inhibitor, FR183998, in anesthetized rats. FR183998 had a potent inhibitory effect on Na+/H+ exchange of rat lymphocytes with median inhibitory (IC50) value of 0.3 nM. Treatment with FR183998 (0.01-0.32 mg/kg, i.v.) reduced or completely abolished ventricular fibrillation and mortality induced by 5-min ischemia followed by reperfusion, when it was administered not only 5 min before ischemia but also 1 min before reperfusion. Myocardial infarct size induced by 30-min ischemia and 60-min reperfusion was reduced significantly in a dose-dependent manner by FR183998 (0.1-1.0 mg/kg, i.v.) when the drug was administered preischemically or at an early phase of ischemia. The ventricular tachycardia and the ventricular fibrillation observed during the ischemic period also were suppressed significantly. These results indicate that FR183998 has a strong inhibitory effect on Na+/H+ exchange and suggest that treatment with FR183998 either before or immediately after the onset of ischemia can prevent the occurrence of arrhythmias and myocardial cell necrosis in situations of ischemia and reperfusion.
Basic Pathologic Processes in the Nervous System

The methods for pathological assessment of the central nervous system and the peripheral nervous system differ, and there are also differences in the level of cellular resolution routinely achieved in screening techniques. In the PNS, plastic-embedded sections and teased nerve fibers from multiple regions provide satisfactory screening techniques; in the CNS, differential staining of paraffin sections provides the most practical screening approach. In both the CNS and PNS, the basic pathological processes are similar; these include Wallerian degeneration, distal axonal degeneration, and primary demyelination. In the future, new screening techniques based on immunocytochemical analyses and measurement of specific mRNA levels can be anticipated.
Gender differences in colorectal polyps and tumors

OBJECTIVES:To use a national endoscopy database (CORI) to determine 1) whether gender differences are noted in the prevalence and location of polyps and tumors; 2) whether women have a higher rate of right-sided polyps or tumors; and 3) whether age influences these results.METHODS:CORI database from April 1, 1997 to February 19, 1999, captured in a computer-generated report, was analyzed. Polyps for this study were defined as sessile or pedunculated and as >9 mm. Tumors were defined as lesions characteristic of adenocarcinoma (mass, apple-core). Pure right-sided colon (PRS) was defined as cecum, ascending, hepatic flexure; right-sided as PRS plus the transverse colon; and left-sided as the splenic flexure, descending, sigmoid and rectum.RESULTS:Men have a greater risk of polyps [odds ratio (OR), 1.5] and tumors (OR, 1.4) than women. The risk of finding polyps and tumors at colonoscopy increases with age, with the highest risk noted in those >69 yr of age relative to patients <50 yr of age (polyps, OR = 2.7; tumors, OR = 4.0). Right-side polyps and pure right-sided polyps as defined by the study design were noted to be more frequent than left-sided polyps in patients >60 yr of age. Women have a greater risk of developing pure right-sided polyps (OR, 1.2), tumors (OR, 1.6) and right-sided tumors (OR, 1.5) than men.CONCLUSIONS:Men have a higher prevalence of colon polyps and tumors than women. A progressive risk of polyp or tumor formation is noted with aging. Women had a greater number of pure right-sided polyps and tumor development. Colonoscopy is needed to correctly diagnose an increasing prevalence of right-sided pathology in the elderly.
Double-stranded RNA induces specific developmental defects in zebrafish embryos.

Treatment with double-stranded RNA (dsRNA) has been shown to interfere with the function of specific genes in various invertebrate species. However, it has not yet been reported that this technique can be applied to vertebrates as well. We have investigated whether dsRNA treatment will inhibit gene function in zebrafish embryos. By microinjecting dsRNA corresponding to three genetically characterised genes we produced embryonic defects that were similar to the known mutant phenotypes of these loci. The efficiency of inducing specific defects (20-30%) was about 10-fold higher than in experiments with antisense RNA. We also observed that the level of the endogenous mRNA in zebrafish embryos was substantially reduced throughout the embryo following dsRNA injection. However, the interference of gene function showed a strong dependence on the amount of dsRNA. These findings suggest that dsRNA-mediated interference will become an important tool for analysing the functional roles of genes in zebrafish and other vertebrates.
High-dose imatinib improves cytogenetic and molecular remissions in patients with pretreated Philadelphia-positive, BCR-ABL-positive chronic phase chronic myeloid leukemia: first results from the randomized CELSG phase III CML 11 “ISTAHIT” study

Background Imatinib 400 mg/day is the standard treatment for patients with chronic phase chronic myeloid leukemia. Recent reports suggested higher and more rapid cytogenetic and molecular responses with higher doses of imatinib. Design and Methods In this prospective international, multicenter phase III study, 227 patients with pre-treated Philadelphia chromosome-positive, BCR-ABL-positive chronic myeloid leukemia were randomized to a standard-dose imatinib arm (400 mg/day) or a high-dose imatinib arm (800 mg/day for 6 months followed by 400 mg/day as maintenance therapy). In this planned interim analysis hematologic, cytogenetic and molecular responses as well as toxicity were evaluated. Results Compared to the standard-dose, high-dose imatinib led to higher rates of major and complete cytogenetic responses at both 3 months (major: 21% versus 37%, P=0.01; complete: 6% versus 25%, P<0.001) and 6 months (major: 34% versus 54%, P=0.009; complete: 20% versus 44%, P<0.001). This was paralleled by a significantly higher major molecular response rate at 6 months in the high-dose imatinib arm (11.8% versus 30.4%; P=0.003). At 12 months, the rates of major cytogenetic response (the primary end-point) were comparable between the two arms (57% versus 59%). In contrast to non-hematologic toxicities, grade 3/4 hematologic toxicities were more common in the high-dose arm. Cumulative complete cytogenetic response rates were higher in patients without dose reduction in the high-dose arm (61%) than in the patients with no dose reduction in the standard-dose arm (36%) (P=0.014). Conclusions This is the first randomized phase III trial in patients with pre-treated chronic phase chronic myeloid leukemia demonstrating improvements in major cytogenetic response, complete cytogentic response and major molecular response rates with high-dose imatinib therapy (ClinicalTrials.gov Identifier: NCT00327262).
A Comparison of Magnetization Transfer Methods to Assess Brain and Cervical Cord Microstructure in Multiple Sclerosis

Demyelination is a core pathological feature of multiple sclerosis (MS) and spontaneous remyelination appears to be an important mechanism for repair in the disease. Magnetization transfer ratio imaging (MTR) has been used extensively to evaluate demyelination, although limitations to its specificity are recognized. MT saturation imaging (MTsat) removes some of the T1 dependence of MTR. We have performed a comparative evaluation of MTR and MTsat imaging in a mixed group of subjects with active MS, to explore their relative sensitivity to pathology relevant to explaining clinical outcomes.
Pegylated Liposomal Doxorubicin: Metamorphosis of an Old Drug into a New Form of Chemotherapy

Pegylated liposomal doxorubicin (Doxil, Caelyx) is a formulation of doxorubicin in poly(ethylene glycol)-coated (stealth) liposomes with a prolonged circulation time and unique toxicity profile. We review the preclinical and clinical pharmacology as well as recent clinical data obtained in specific cancer types. Doxil liposomes retain the drug payload during circulation and accumulate preferentially in tissues with increased microvascular permeability, as often is the case of tumors. Doxil toxicity profile is drastically different from that of doxorubicin, and is characterized by dominant and dose-limiting mucocutaneous toxicities, mild myelosupression, minimal alopecia, and no apparent cardiac toxicity. Although the single maximum tolerated dose (MTD) of Doxil is actually lower than that of conventionally administered doxorubicin, the cumulative MTD dose of Doxil may be substantially greater than that of free doxorubicin. Doxil is probably one of the most active agents in AIDS-related Kaposi's sarcoma and has a definite role in management of recurrent ovarian cancer. The potential of Doxil in the treatment of other cancer types and the opportunities it offers in combination with other drugs and therapeutic modalities are under active investigation.
Genetic association studies of ACE and PAI-1 genes in women with recurrent pregnancy loss

Summary A fine balance between coagulation and fibrinolysis is critical in early pregnancy. Plasminogen activator inhibitor-1 (PAI-1) and angiotensin converting enzyme (ACE) are involved in the fibrinolytic process, and several studies have reported the association between their gene polymorphisms and recurrent pregnancy loss (RPL). This study was conducted to investigate the association between PAI-1 and ACE polymorphisms and idiopathic RPL, using meta-analyses. A systematic review of the published literature from the MEDLINE and EMBASE databases before April 2012 was conducted. Of 209 potentially relevant studies, 22 case-control studies comprising a total of 2,820 RPL patients and 3,009 controls were included. Among these studies were 11 reports of PAI-1 4G/5G and 11 of ACE I/D polymorphisms in patients with RPL. A significant association was found withthe ACE I/D polymorphism [summary odds ratio 1.29 (95% confidence interval 1.02–1.62)] in studies including more than two recurrent abortions. Subgroup analysis did not show significant associations with RPL in Caucasian and non-Caucasian patients. Meta-analyses of PAI-1 4G/5G polymorphism were not found associations with RPL in studies including more than two or three recurrent abortions, and in studies of Caucasian and non-Caucasian patients. In conclusion, meta-analyses showed a significant association between the ACE I/D polymorphism and idiopathic RPL. High clinical heterogeneity existed among studies of PAI-1 4G/5G, and the aggregated data failed to confer higher susceptibility to idiopathic RPL. More well-designed studies with different ethnic populations are required for future integration.
On power efficient communication over multi-hop wireless networks: joint routing, scheduling and power control

With increasing interest in energy constrained multi-hop wireless networks (Bambos, N. et al., 1991), a fundamental problem is one of determining energy efficient communication strategies over these multi-hop networks. The simplest problem is one where a given source node wants to communicate with a given destination, with a given rate over a multi-hop wireless network, using minimum power. Here the power refers to the total amount of power consumed over the entire network in order to achieve this rate between the source and the destination. There are three decisions that have to be made (jointly) in order to minimize the power requirement. (1) The path(s) that the data has to take between the source and the destination. (Routing). (2) The power with each link transmission is done. (Power Control). (3) Depending on the interference or the MAC characteristics, the time slots in which specific link transmissions have to take place. (Scheduling). (4) To the best of our knowledge, ours is the first attempt to derive a performance guaranteed polynomial time approximation algorithm for jointly solving these three problems. We formulate the overall problem as an optimization problem with non-linear objective function and non-linear constraints. We then derive a polynomial time 3-approximation algorithm to solve this problem. We also present a simple version of the algorithm, with the same performance bound, which involves solving only shortest path problems and which is quite efficient in practice. Our approach readily extends to the case where there are multiple source-destination pairs that have to communicate simultaneously over the multi-hop network.
Stability and Relapse of Dental Arch Alignment*

For more than 35 years, research in the Department of Orthodontics, University of Washington has focused on a growing collection of over 600 sets of patient records to assess stability and failure of orthodontic treatment. All had completed treatment a decade or more prior to the last set of data. Evaluation of treated premolar extraction cases, treated non-extraction cases with generalized spacing, cases treated by arch enlargement strategies, and untreated normal occlusions demonstrate similar physiological changes. 1. Arch length reduces following orthodontic treatment, but also does so in untreated normal occlusions. 2. Arch width measured across the mandibular canine teeth typically reduces post-treatment whether the case was expanded during treatment or not. 3. Mandibular anterior crowding during the post-treatment phase is a continuing phenomenon well into the 20–40 age bracket and likely beyond. 4. Third molar absence or presence, impacted or fully erupted, seems to have little effect on the occurrence or degree of relapse. 5. The degree of post-retention anterior crowding is both unpredictable and variable and no pretreatment variables either from clinical findings, casts, or cephalometric radiographs before or after treatment seem to be useful predictors.
Generating new service concepts based on ontology integration

Despite the fact that the service concept generation is considered as a key factor for success of new service development, relatively little attention has been paid to how to generate new service concepts. In response, this paper proposes a novel approach to generation of new service concepts based on ontology integration. Since ontology aims to capture the specification of concepts in a specific domain, knowledge set of a domain composed of concept network with various descriptions and relationships can be derived. In addition, creative combination of concepts and relationships between different domains can be generated by integrating ontologies, which makes new service concepts to be generated. Thus, proposed approach suggests how to generate the new service concepts using ontology integration with three steps - construction of service concept ontology, integration of ontologies, and generation of new service concepts. The proposed approach is expected to help service managers to understand the structure of currently provided services and identify candidate service concepts to be generated, thus generate the new service concepts.
A dementia care management intervention: which components improve quality?

OBJECTIVES To analyze whether types of providers and frequency of encounters are associated with higher quality of care within a coordinated dementia care management (CM) program for patients and caregivers. DESIGN Secondary analysis of intervention-arm data from a dementia CM cluster-randomized trial, where intervention participants interacted with healthcare organization care managers (HOCMs), community agency care managers (CACMs), and/ or healthcare organization primary care providers (HOPCPs) over 18 months. METHODS Encounters of 238 patient/caregivers (dyads) with HOCMs, CACMs, and HOPCPs were abstracted from care management electronic records. The quality domains of assessment, treatment, education/support, and safety were measured from medical record abstractions and caregiver surveys. Mean percentages of met quality indicators associated with exposures to each provider type and frequency were analyzed using multivariable regression, adjusting for participant characteristics and baseline quality. RESULTS As anticipated, for all 4 domains, the mean percentage of met dementia quality indicators was 15.5 to 47.2 percentage points higher for dyads with HOCM--only exposure than for dyads with none (all P < .008); not anticipated were higher mean percentages with increasing combinations of provider-type exposure-up to 73.7 percentage points higher for safety (95% confidence interval 65.2%-82.1%) with exposure to all 3 provider types compared with no exposure. While greater frequency of HOCM-dyad encounters was associated with higher quality (P < .04), this was not so for other provider types. CONCLUSIONS HOCMs' interactions with dyads was essential for dementia care quality improvement. Additional coordinated interactions with primary care and community agency staff yielded even higher quality.
Free radical reactions of isoxazole and pyrazole derivatives of hispolon: kinetics correlated with molecular descriptors

Abstract Hispolon (HS), a natural polyphenol found in medicinal mushrooms, and its isoxazole (HI) and pyrazole (HP) derivatives have been examined for free radical reactions and in vitro antioxidant activity. Reaction of these compounds with one-electron oxidant, azide radicals () and trichloromethyl peroxyl radicals (), model peroxyl radicals, studied by nanosecond pulse radiolysis technique, indicated formation of phenoxyl radicals absorbing at 420 nm with half life of few hundred microseconds (μs). The formation of phenoxyl radicals confirmed that the phenolic OH is the active centre for free radical reactions. Rate constant for the reaction of these radicals with these compounds were in the order kHI ≅ kHP > kHS. Further the compounds were examined for their ability to inhibit lipid peroxidation in model membranes and also for the scavenging of 2,2′-diphenyl-1-picrylhydrazyl (DPPH) radical and superoxide () radicals. The results suggested that HP and HI are less efficient than HS towards these radical reactions. Quantum chemical calculations were performed on these compounds to understand the mechanism of reaction with different radicals. Lower values of adiabatic ionization potential (AIP) and elevated highest occupied molecular orbital (HOMO) for HI and HP compared with HS controlled their activity towards and radicals, whereas the contribution of overall anion concentration was responsible for higher activity of HS for DPPH, , and lipid peroxyl radical. The results confirm the role of different structural moieties on the antioxidant activity of hispolon derivatives.
Technical Debt

We report here on the Eighth International Workshop on Managing Technical Debt, collocated with the International Conference on Software Maintenance and Evolution (ICSME 2016). The technical debt research community continues to expand through collaborations of industry, tool vendors, and academia. The major themes of discussion this year indicate convergence on a common definition on technical debt and its elements which drive the maturation of a research roadmap, demonstrating that managing technical debt is a mainstream topic in software engineering research bringing empirical analysis, data science, software design and architecture analysis and automation among other challenges together.
PAI‐1 gene 4G/5G genotype: A risk factor for thrombosis in vessels of internal organs

Although the common 4G/5G polymorphism in the promoter of the PAI‐1 gene was suggested to be a risk factor for some of the thrombotic disorders, its significance in the development of thrombosis is still controversial. This study presents the data on a total of 357 patients with different types of thrombosis and 281 unrelated healthy controls. It was found that the 4G/4G genotype is associated with a higher risk of thrombosis (OR, 1.7; 95% CI, 1.1–2.5). Patients were divided into five distinct groups according to the site of thrombosis. Both 4G/4G and 4G/5G genotypes were associated with a higher risk of thrombosis development in a group of 69 patients with internal organ thrombosis (OR, 6.35; 95% CI, 2.5–16.1 and OR, 4.85; 95% CI, 2.0–12.1, respectively). Interestingly, this association was even stronger in a subgroup of 33 patients with portal vein thrombosis (PVT) and 4G/4G and 4G/5G genotypes conferred more than 10‐ and 6‐fold increases in the risk of developing PVT (95% CI: 2.3–47.1 and 1.4–28.8), respectively. No statistically significant association was found between 4G/4G genotype and the groups of deep vein thrombosis (126 patients), cerebral thrombosis (80 patients), retinal thrombosis (72 patients), and purpura fulminans (16 patients). Factor V Leiden or prothrombin G20210A mutations did not emerge as additional risk factors for thrombosis in any of the groups studied. To conclude, this study suggests that there may be an association between 4G/4G and 4G/5G genotypes and the thrombosis in vessels of internal organs especially in the portal veins. Am. J. Hematol. 71:89–93, 2002. © 2002 Wiley‐Liss, Inc.