Miracle-dz/UniFAR-FTUs huggingface dataset:
Prognostic significance of cyclooxygenase 2 expression in 259 cases of non-small cell lung cancer.

CONTEXT Previous studies report that increased expression of cyclooxygenase 2 (COX-2) correlates with poor clinical outcome in several malignancies, including non- small cell lung carcinoma (NSCLC). Cyclooxygenase 2 inhibitors have been reported to effectively inhibit carcinogenesis in colon cancer experimental models. OBJECTIVE We examined COX-2 expression in 259 cases of NSCLC to evaluate its prognostic significance. DESIGN Sections of NSCLC from patients with a median 5-year follow-up were immunostained with COX-2 monoclonal antibody (1:150) using the Dako mouse EnVision;pl system. Extent of COX-2 expression in neoplastic cells was recorded as follows: 0, 0% to 10% of cells positive; 1, 11% to 33% positive; 2, 34% to 66% positive; and 3, more than 66% positive. Intensity was scored as either increased (+) or not increased (-), compared to internal control smooth muscle and endothelial cells. Kaplan-Meier analysis was used to assess the relationship between survival and COX-2 expression, using the log-rank test for statistical significance. RESULTS No relationship was found between the extent and/or the intensity of COX-2 expression and patient survival when the entire cohort was considered. However, when separately analyzed according to disease stage and intensity of COX-2 expression, a significant relationship (P = .03) between increased COX-2 expression and shortened patient survival was found only in patients with stage I and II NSCLC. CONCLUSIONS To our knowledge, this is the largest series of NSCLCs in which COX-2 has been investigated as a prognostic marker. The findings in this large series support previous studies of smaller cohorts that reported that increased COX-2 expression predicts poor outcome in patients with early-stage NSCLC.
Efficacy and Safety of Vorapaxar in Patients With Prior Ischemic Stroke

Background and Purpose— Vorapaxar is an antiplatelet agent that antagonizes thrombin-mediated activation of the protease-activated receptor-1 on platelets. We tested the efficacy and safety of vorapaxar in a prespecified analysis in the stroke subcohort from a multinational, randomized, placebo-controlled trial. Methods— We randomly assigned patients with prior atherothrombosis (myocardial infarction, peripheral artery disease, or ischemic stroke) to receive vorapaxar (2.5 mg daily) or placebo added to standard antiplatelet therapy. Patients who qualified with stroke (N=4883) had a history of ischemic stroke in the prior 2 weeks to 12 months. The primary end point was the composite of cardiovascular death, myocardial infarction, or any stroke. Results— The qualifying stroke was classified as large vessel in 35%, small vessel in 47%, and other/unknown in 18%. In the stroke cohort, cardiovascular death, myocardial infarction, or stroke through 3 years was not reduced with vorapaxar versus placebo (13.0% vs 11.7%; hazard ratio, 1.03; 95% confidence interval, 0.85–1.25), including recurrent ischemic stroke (hazard ratio, 0.99; 95% confidence interval, 0.78–1.25). There were no significant differences in the effect of vorapaxar based on the type or timing of the qualifying stroke. Intracranial hemorrhage at 3 years was increased with vorapaxar (2.5% vs 1.0%; hazard ratio, 2.52; 95% confidence interval, 1.46–4.36). Conclusions— In patients with prior ischemic stroke who receive standard antiplatelet therapy, adding vorapaxar increased the risk of intracranial hemorrhage without an improvement in major vascular events, including ischemic stroke. These findings add to the accumulating evidence establishing important risks with combination antiplatelet therapy in patients with prior stroke. Clinical Trial Registration Information— http://www.clinicaltrials. gov. Unique identifier: NCT00526474.
Clinical Examination of Tissue Eosinophilia in Patients with Chronic Rhinosinusitis and Nasal Polyposis

Objective (1) Describe clinical and histopathologic findings in patients with chronic rhinosinusitis with nasal polyps (CRSwNP). (2) Determine if tissue and serum eosinophilia predicts disease severity in CRSwNP. Study Design Case series with chart review. Setting Academic hospital specializing in respiratory and allergic disease. Subjects Patients with CRSwNP treated from 2008 to 2010. Methods Clinical data were collected; sinus computed tomography (CT) scans were scored according to the Lund-Mackay system; and surgical specimens were evaluated for degree of tissue eosinophilia. Statistical analysis was performed to compare eosinophilia with indicators of disease severity. Results Seventy CRSwNP patients were included, with a mean Lund-Mackay score of 16.7; 62.1% of patients had severe asthma, and 62.9% were aspirin sensitive. Elevated tissue eosinophil level did not correlate with medication usage, olfactory symptoms, or Lund-Mackay scores, nor did it correlate with presence of asthma or aspirin-sensitivity (P = .09). Patients with mild asthma had significantly more tissue eosinophils versus patients with severe asthma, possibly because of the high amount of chronic corticosteroid use in severe asthmatics. There was no correlation between tissue and serum eosinophil counts (P = .97), but there was a significant positive correlation between CT score and peripheral eosinophil level (P < .05). Conclusions Higher serum eosinophil levels may indicate more extensive mucosal disease as measured on CT scan. Neither serum nor tissue eosinophilia predicted disease severity in our retrospective analysis of CRSwNP patients, and serum eosinophil level did not serve as a marker of tissue eosinophilia.
Primary structure of colicin M, an inhibitor of murein biosynthesis

The DNA sequence of the colicin M activity gene cma was determined. A polypeptide consisting of 271 amino acids was deduced from the nucleotide sequence. The amino acid sequence agreed with the peptide sequences determined from the isolated colicin. The molecular weight of active colicin M was 29,453. The primary translation product was not processed. In the domain required for uptake into cells, colicin M contained the pentapeptide Glu-Thr-Leu-Thr-Val. A similar sequence was found in all colicins which are taken up by a TonB-dependent mechanism and in outer membrane receptor proteins which are constituents of TonB-dependent transport systems. The structure of colicin M in the carboxy-terminal activity domain had no resemblance to the pore-forming colicins or colicins with endonuclease activity. Instead, the activity domain contained a sequence which exhibited homology to the sequence around the serine residue in the active site of penicillin-binding proteins of Escherichia coli. The colicin M activity gene was regulated from an SOS box upstream of the adjacent colicin B activity gene on the natural plasmid pColBM-Cl139.
Corticosteroid-Induced Asthma: A Manifestation of Limited Hyperinfection Syndrome Due to Strongyloides stercoralis

Inadequate therapeutic response to parenteral corticosteroids in patients with acute bronchial asthma is infrequent. We report four patients whose bronchial asthma symptoms worsened after treatment with parenteral corticosteroids. All had larvae of Strongyloides stercoralis in the stool. The new attack or the exacerbation of asthma appeared to be precipitated by systemic corticosteroid administration. The paradoxic therapeutic response of asthma to glucocorticoids was the major pulmonary manifestation of Strongyloides superinfection; there was no evidence of other organ involvement. Individuals with new onset of bronchial asthma or worsening of asthmatic episodes concurrent with the use of systemic corticosteroids should have thorough investigation for possible superinfection due to Strongyloides stercoralis. This is particularly important for patients who have resided in areas where intestinal helminthic infections are endemic. Discontinuance of steroid therapy or reduction in dosage of parenteral steroids appears necessary. Treatment with thiabendazole appears to be effective in patients with limited hyperinfection syndrome.
Cellular mechanisms involved in the melatonin inhibition of HT‐29 human colon cancer cell proliferation in culture

Abstract: The antiproliferative and proapoptotic properties of melatonin in human colon cancer cells in culture were recently reported. To address the mechanisms involved in these actions, HT‐29 human colon cancer cells were cultured in RPMI 1640 medium supplemented with fetal bovine serum at 37°C. Cell proliferation was assessed by the incorporation of [3H]‐thymidine into DNA. Cyclic nucleotide levels, nitrite concentration, glutathione peroxidase and reductase activities, and glutathione levels were assessed after the incubation of these cells with the following drugs: melatonin membrane receptor agonists 2‐iodo‐melatonin, 2‐iodo‐N‐butanoyl‐5‐methoxytryptamine, 5‐methoxycarbonylamino‐N‐acetyltryptamine (GR‐135,531), and the antagonists luzindole, 4‐phenyl‐2‐propionamidotetralin, and prazosin; the melatonin nuclear receptor agonist CGP 52608, and four synthetic kynurenines analogs to melatonin 2‐acetamide‐4‐(3‐methoxyphenyl)‐4‐oxobutyric acid, 2‐acetamide‐4‐(2‐amino‐5‐methoxyphenyl)‐4‐oxobutyric acid, 2‐butyramide‐4‐(3‐methoxyphenyl)‐4‐oxobutyric acid and 2‐butyramide‐4‐(2‐amino‐5‐methoxyphenyl)‐4‐oxobutyric acid. The results show that the membrane receptors are not necessary for the antiproliferative effect of melatonin and the participation of the nuclear receptor in this effect is suggested. Moreover, the antioxidative and anti‐inflammatory actions of melatonin, counteracting the oxidative status and reducing the production of nitric oxide by cultured HT‐29 cells seem to be directly involved in the oncostatic properties of melatonin. Some of the synthetic kynurenines exert higher antiproliferative effects than melatonin. The results reinforce the clinical interest of melatonin due to the different mechanisms involved in its oncostatic role, and suggest a new synthetic pathway to obtain melatonin agonists with clinical applications to oncology.
Patients' attitudes to the use of placebos: results from a New Zealand survey.

AIMS To examine how amenable patients are to the use of placebos in clinical practice, their willingness to participate in a placebo-controlled clinical trial (PCT), and to examine patients' beliefs about the placebo effect. METHODS A cross-sectional questionnaire survey was administered to 211 general practice patients of two primary care clinics in socioeconomically divergent areas of the Auckland region, New Zealand. The questionnaire obtained self-report of willingness to accept various clinical uses of placebo as measured by the Attitudes to Placebo Treatments Scale (APTS), willingness to participate in a PCT including reasons for or against participation, and beliefs about the placebo effect. RESULTS The APTS score (M=22.34, SD=7.93) for the entire sample showed that patients were accepting of placebo use in certain clinical situations, even the use of placebo as a diagnostic tool. Patients seem to consider placebo use more appropriate when it is for the benefit of the patient, at the patient's request, or when there seems to be no available alternate treatment. Placebo use was considered inappropriate when its use was seen to be for the benefit(s) of the physician or where placebo use seemed dangerous. 59% of the patients surveyed indicated willingness to participate in a PCT. CONCLUSION Many patients are amenable to the use of placebos, suggesting that the major issues of placebo use (deception and lack of informed consent) are tolerated by the patients surveyed. Many were prepared to participate in a PCT particularly in order to support the development of new treatment and help other patients. However, patients seem to have misguided beliefs about the placebo effect, underestimating the effectiveness of the placebo and attributing placebo effects to personality. Generally, patients lack understanding of the placebo effect.
[Trabeculectomy Ab Interno in Primary Open Angle Glaucoma and Exfoliative Glaucoma].

BACKGROUND To assess the outcome of routine trabectomy surgery in the treatment of primary (POAG) and secondary open angle glaucoma. PATIENTS/METHODS 296 eyes of 296 patients with diagnosed open angle glaucoma and exfoliative glaucoma were analysed from June 2012 until June 2014. IOP readings (intraocular pressure) and the number of antiglaucoma medications was evaluated at every follow-up visit. For statistical analysis, 4 study cohorts were built (cohort 1 = trabectomy in POAG, cohort 2 = trabectomy in exfoliative glaucoma (PEX), cohort 3 = trabectomy + IOL in POAG, cohort 4 = trabectomy + IOL in PEX glaucoma). RESULTS Mean IOP before trabectomy surgery was 19.8 ± 5.9 mmHg and 23.7 ± 9.5 mmHg in cohorts 1 and 2, respectively. At 1 year follow-up, IOP was reduced to normal level for cohorts 1 and 2 (14.8 ± 3.2 mmHg (p = 0.001) and 14.0 ± 3.3 mmHg (p = 0.046), respectively). The number of topical antiglaucoma medications changed to 2.1 ± 1.2 (p = 0.004) and 2.4 ± 1.2, respectively (p = 0.593) at one year follow-up, respectively, for POAG and exfoliative glaucoma. In study cohort 3 and 4, mean IOP before trabectomy surgery was 19.2 ± 4.0 mmHg and 23.2 ± 9.2 mmHg, respectively. At 1 year follow-up, IOP was reduced to normal levels in cohorts 3 and 4 (11.8 ± 3.1 mmHg (p < 0.01) and 12.6 ± 1.1 mmHg, respectively (p = 0.043)); the number of topical antiglaucoma medications changed to 2.3 ± 1.4 (p = 0.469) and 1.4 ± 0.8, respectively, (p = 0.102) at 1 year follow-up. A significant difference in IOP reduction could be demonstrated in POAG between the trabectomy + IOL group and the trabectomy cohort 1 year postoperative (p = 0.017); in the PEX trabectomy + IOL versus PEX trabectomy cohort no statistically significant difference (p = 0.678) could be demonstrated. No serious postoperative complications were recorded. CONCLUSION Trabectomy surgery seemed to be a reliable and effective tool for the management of mild and moderate primary and secondary open angle glaucoma with uncontrolled IOP in daily routine. One year follow-up showed a significant reduction in intraocular pressure in all cohorts.
On the Relation between the Mental Number Line and Arithmetic Competencies

In this study, we aimed at investigating whether it is indeed the spatial magnitude representation that links number line estimation performance to other basic numerical and arithmetic competencies. Therefore, estimations of 45 fourth-graders in both a bounded and a new unbounded number line estimation task (with only a start-point and a unit given) were correlated with their performance in a variety of tasks including addition, subtraction, and number magnitude comparison. Assuming that both number line tasks assess the same underlying mental number line representation, unbounded number line estimation should also be associated with other basic numerical and arithmetic competencies. However, results indicated that children's estimation performance in the bounded but not the unbounded number line estimation task was correlated significantly with numerical and arithmetic competencies. We conclude that unbounded and bounded number line estimation tasks do not assess the same underlying spatial–numerical representation. Rather, the observed association between bounded number line estimation and numerical/arithmetic competencies may be driven by additional numerical processes (e.g., proportion judgement, addition/subtraction) recruited to solve the task.
Towards a theory of local Shimura varieties

This is a survey article that advertises the idea that there should exist a theory of p-adic local analogues of Shimura varieties. Prime examples are the towers of rigid-analytic spaces defined by Rapoport-Zink spaces, and we also review their theory in the light of this idea. We also discuss conjectures on the l-adic cohomology of local Shimura varieties.
Alteration of Activation, Growth, and Atresia of Bovine Preantral Follicles by Long-Term Treatment of Cows with Estradiol and Recombinant Bovine Somatotropin

Abstract The hypothesis was that long-term treatment of cattle with estradiol (E2) and bovine somatotropin (bST) would alter the earliest stages of folliculogenesis. Nonlactating Holstein cows (n = 26) were treated in a 2 × 2 arrangement with E2 (2 × 24 mg implants, 67.1 ± 1.4 days) and bST (Posilac, 63.6 ± 1.5 days). At Day 67 ± 1.3, one ovary was removed for morphometric and immunohistochemical analysis. For each ovary, 388 ± 38 microscopic fields (2 × 2 mm) were examined and follicles within each field were classified by histological stage. Fields that contained no follicles were classified as empty. Empty fields (n = 100 per ovary) were further classified as containing no evidence of follicles or containing atretic remnants of follicles. Approximately 30 4-μm sections per ovary were stained for proliferating cell nuclear antigen (PCNA), and 150 fields per ovary were evaluated. Additional sections (n = 10 per ovary) were assessed immunohistochemically for apoptosis, and fluorescence intensity was determined for each follicle. Treatment with bST significantly decreased percentage of empty fields containing atretic remnants. Treatment with E2 induced activation of follicles as shown by a decrease in percentage of primordial follicles and an increase in percentage of primary follicles as determined by PCNA staining. At the primary follicle stage the combination of bST + E2 decreased apoptosis as shown by decreased fluorescence intensity. Thus, E2 induced activation of follicles, bST enhanced survival, and the combination lowered atresia.
Price based unit commitment for Gencos in deregulated markets

Some power markets require the Gencos to bid for each individual generator rather than for a group of units. So, it may be desirable to develop unit commitment and generation schedule strategies for individual units. This paper presents a technique to optimize the unit commitment and generation schedules on the basis of the forecasted price. A methodology based on dynamic programming and enumeration has been proposed. The technique has further been extended to optimize the problem for a group of generators. The technique is explained with illustrative examples and then applied to several systems reported in the literature. The results obtained are very encouraging, comparable, if not better, than the results reported earlier in all cases. Finally, the proposed technique is quite simple and requires significantly less computational time.
Activation of a Novel Transcription Factor through Phosphorylation by WIPK, a Wound-Induced Mitogen-Activated Protein Kinase in Tobacco Plants1

Wound-induced protein kinase (WIPK) is a tobacco (Nicotiana tabacum) mitogen-activated protein kinase known to play an essential role in defense against wounding and pathogens, although its downstream targets have yet to be clarified. This study identified a gene encoding a protein of 648 amino acids, which directly interacts with WIPK, designated as N. tabacum WIPK-interacting factor (NtWIF). The N-terminal region with approximately 250 amino acids showed a high similarity to the plant-specific DNA binding domain, B3, but no other similarity with known proteins. The C terminus of approximately 200 amino acids appeared to be essential for the interaction with WIPK, and a Luciferase-reporter gene assay using Bright Yellow 2 cells indicated the full-length protein to possess trans-activation activity, located to the middle region of approximately 200 amino acids. In vitro phosphorylation assays indicated that WIPK efficiently phosphorylates the full-length protein and the N terminus but not the C terminus. When full-length NtWIF was coexpressed with WIPK in Bright Yellow 2 cells, the Luciferase transcriptional activity increased up to 5-fold that of NtWIF alone, whereas no effect was observed with a kinase-deficient WIPK mutant. Transcripts of NtWIF began to simultaneously accumulate with those of WIPK 30 min after wounding and 1 h after the onset of hypersensitive response upon tobacco mosaic virus infection. These results suggest that NtWIF is a transcription factor that is directly phosphorylated by WIPK, thereby being activated for transcription of target gene(s) involved in wound and pathogen responses.
Mechanistic Aspects in the Formation, Growth and Surface Functionalization of Metal Oxide Nanoparticles in Organic Solvents.

The synthesis of metal oxide nanoparticles in organic solvents, so-called nonaqueous (or nonhydrolytic) processes represent powerful alternatives to aqueous approaches and have become an independent research field. 10 Years ago, when we published our first review on organic reaction pathways in nonaqueous sol-gel approaches, the number of examples was relatively limited. Nowadays, it is almost impossible to provide an exhaustive overview. Here we review the development of the last few years, without neglecting pioneering examples, which help to follow the historical development. The importance of a profound understanding of mechanistic aspects of nanoparticle crystallization and formation mechanisms can't be overestimated, when it comes to the design of rational synthesis concepts under minimization of trial-and-error experiments. The main reason for the progress in mechanistic understanding lies in the availability of characterization tools that make it possible to monitor chemical reactions from the dissolution of the precursor to the nucleation and growth of the nanoparticles, by ex situ methods involving sampling after different reaction times, but more and more also by in situ studies. After a short introduction to experimental aspects of nonaqueous sol-gel routes to metal oxide nanoparticles, we provide an overview of the main and basic organic reaction pathways in these approaches. Afterwards, we summarize the main characterization methods to study formation mechanisms, and then we discuss in great depth the chemical formation mechanisms of many different types of metal oxide nanoparticles. The review concludes with a paragraph on selected crystallization mechanisms reported for nonaqueous systems and a few illustrative examples of nonaqueous sol-gel concepts applied to surface chemistry.
Sleep problems, psychiatric hospitalization, and emergency department use among psychiatric patients with Medicaid.

OBJECTIVE This study examined the prevalence of sleep problems and their association with the use of inpatient and emergency department services by Medicaid recipients with serious mental illness. METHODS The sample consisted of 1,560 psychiatric patients with Medicaid coverage who were identified in a ten-state random survey of psychiatrists. Sleep problems were assessed by clinician ratings. RESULTS Over 75% of the patients experienced a sleep problem, and approximately 50% of these patients had problems that were moderate to severe. Greater sleep problem severity was associated with an increased risk of psychiatric hospitalization and emergency department visits for mental health reasons. CONCLUSIONS Sleep problems were highly prevalent among Medicaid patients with serious mental illness and were associated with greater inpatient and emergency mental health service use. More careful monitoring and management of sleep problems in this patient population could address a common clinical need and might help to reduce costly service use.