LLukas22/scidocs huggingface dataset:
Minichromosome maintenance (Mcm) proteins, cyclin B1 and D1, phosphohistone H3 and in situ DNA replication for functional analysis of vulval intraepithelial neoplasia

Vulval intraepithelial neoplasia (VIN) is defined histopathologically by distinctive abnormalities of cellular maturation and differentiation. To investigate the functional properties of VIN, the expression of several proteins involved in the regulation of the cell cycle as well as in situ DNA replication competence was analysed by immunohistochemistry. Snap-frozen vulval biopsies were graded as normal squamous epithelium (n=6), undifferentiated HPV positive VIN 1 (n=3), VIN 2 (n=8) and VIN 3 (n=20). Immunohistochemistry was performed using the following markers: cyclin D1 (expressed in middle/late G1), cyclin B1 (expressed in G2/early M), phosphorylated histone H3 (expressed during mitosis) and minichromosome maintenance (Mcm) proteins 2 and 5 (expressed during the cell cycle, but not in differentiated or quiescent cells). In situ DNA replication competence was used to identify S-phase cells. The percentage of positively stained nuclei in three representative microscopic fields was calculated per biopsy. In normal vulva, the expression of all markers was restricted to the proliferative compartment of the basal layer of the epithelium. In contrast in high-grade VIN, the majority of epithelial cells expressed the Mcm proteins from basal to superficial layer. The detection of cyclins B1 and D1, phospho-histone H3 and in situ DNA replication was also found through the full thickness of these lesions but by a lower proportion of the cells. This is consistent with these markers providing a series of ‘snapshots’ of the cell cycle status of individual cells. The low-grade VIN showed reduced expression of the cell cycle markers in relation to the level of dysplasia. The combination of these analyses establishes that the majority of VIN cells remain in a functional replicative or prereplicative state of the cell cycle. Clinical application of these analyses may provide a basis for improved diagnosis of VIN.
Nanocrystallization and hydrogen storage in rapidly solidified Mg–Ni–RE alloys

Abstract Hydrogen storage in rapidly solidified magnesium based Mg–Ni–RE (RE=Y or Mm) alloys was studied. The as-quenched alloys were amorphous or nano-/amorphous, consisting of nanocrystals (with average size of 3 nm) embedded in large amounts of amorphous phase. The hydrogenation properties (hydrogen storage capacity and hydrogenation kinetics) of Mg 76 Ni 19 Y 5 and Mg 78 Ni 18 Y 4 alloys were compared mainly with those of Mg 75 Ni 20 Mm 5 (Mm=Ce, La-rich mischmetal), reported recently. Alloys with the above mentioned compositions were found to attain the best hydriding characteristics among the Mg–Ni–RE alloys. A more beneficial effect on the hydrogen storage capacity of Mm (La,Ce-rich mischmetal) than Y was detected. Crystallization of these alloys leads to a nanocrystalline material through a metastable fcc Mg 6 Ni phase, as for the Mg 78 Ni 18 Y 4 alloy the nanostructure and the intermediate phase are thermally more stable. The kinetics of crystallization was studied at non-isothermal conditions and the kinetic parameters for different magnesium alloys were compared. The results from previous and the present study show that stable nanocrystalline microstructures appropriate for hydrogen storage can be produced by controlled crystallization of amorphous or nano-/amorphous magnesium based Mg–Ni–RE precursors.
Time Trends and Impact of Upper and Lower Gastrointestinal Bleeding and Perforation in Clinical Practice

OBJECTIVES:Changing patterns in medical practice may contribute to temporal changes in the incidence of upper and lower gastrointestinal (GI) complications. There are limited data on the incidence of lower GI complications in clinical practice and most studies that have been done have serious methodological limitations to inferring the actual burden of this problem. The aims of this study were to analyze time trends of hospitalizations resulting from GI complications originating both from the upper and lower GI tract in the general population, and to determine the risk factors, severity, and clinical impact of these GI events.METHODS:This was a population-based study of patients hospitalized because of GI complications in 10 general hospitals between 1996 and 2005 in Spain. We report the age- and gender-specific rates, estimate the regression coefficients of the upper and lower GI event trends, and evaluate the severity and associated risk factors. GI hospitalization charts were validated by an independent review of large random samples of unspecific and specific codes distributed among all hospitals and study years.RESULTS:Upper GI complications fell from 87/100,000 persons in 1996 to 47/100,000 persons in 2005, whereas lower GI complications increased from 20/100,000 to 33/100,000. Overall, mortality rates decreased, but the case fatality remained constant over time. Lower GI events had a higher mortality rate (8.8 vs. 5.5%), a longer hospitalization (11.6±13.9 vs. 7.9±8.8 days), and higher resource utilization than did upper GI events. The use of nonsteroidal anti-inflammatory drugs (NSAIDs) without concomitant proton pump inhibitor was more frequently recorded among upper GI complications than among lower GI complications. When comparing upper GI events with lower GI events, we found that male gender (adjusted odds ratio (OR): 1.94; 95% confidence interval (CI): 1.70–2.21), and recorded NSAID use (OR: 1.92; 95% CI: 1.60–2.30) were associated to a greater extent with upper GI events, whereas older age (OR: 0.83; 95% CI: 0.77–0.89), number of comorbidities (OR: 0.91; 95% CI: 0.86–0.96), and having a diagnosis in recent years (OR: 0.92; 95% CI: 0.90–0.94) were all associated to a greater extent with lower GI events than with upper GI events after adjusting for age, sex, hospitalization, and discharge year.CONCLUSIONS:Over the past decade, there has been a progressive change in the overall picture of GI events leading to hospitalization, with a clear decreasing trend in upper GI events and a significant increase in lower GI events, causing the rates of these two GI complications to converge. Overall, mortality has also decreased, but the in-hospital case fatality of upper or lower GI complication events has remained constant. It will be a challenge to improve future care in this area unless we develop new strategies to reduce the number of events originating in the lower GI tract, as well as reducing their associated mortality.
Universal banking, control rights, and corporate finance in Germany

(1997) and the references therein for more information on the Japanese system of corporate governance. C orporate governance mechanisms assure investors in corporations that they will receive adequate returns on their investments (Shleifer and Vishny, 1997, p. 737). If these mechanisms did not exist or did not function properly, outside investors would not lend to firms or buy equity in them. Businesses would be forced to rely entirely on their own internally generated cash flows and accumulated financial resources to finance ongoing operations as well as profitable investment opportunities. Overall economic performance would suffer because many good business opportunities would be missed and temporary financial problems at individual firms would spread quickly to employees, consumers, and other firms. Despite their universal importance and a considerable international exchange of ideas and institutions, corporate governance systems differ, even among advanced market economies. Useful generalizations can be drawn, however, and researchers commonly differentiate between two leading corporate governance systems (Shleifer and Vishny, 1997, p. 737): (1) the " Anglo-Saxon " model found in the United States, the United Kingdom, and other English-speaking countries, and (2) the " German-Japanese " model found in the two countries named and, to varying degrees, in other countries that share historical or economic traditions with them. Two important dimensions along which these leading corporate governance systems differ are the role of financial markets and the influence of workers on corporate decision making. Financial markets are important sources of corporate finance and corporate governance in countries operating under the Anglo-Saxon model. Public and private markets for debt and equity securities issued by corporations outstrip the amount of financing provided directly by financial intermediaries by a wide margin. Many firms change hands each year on the stock market, some without the consent of incumbent management (i.e., via hostile takeovers). Meanwhile, employees' influence on matters of corporate governance is very diffused, exercised primarily through union representation and a limited amount of equity ownership in pension or personal savings plans. Firms in which non-executive workers play a meaningful role in corporate decision making are the exception rather than the rule in these economies. 1 Capital allocation and corporate gov-ernance practices in countries operating under the German-Japanese model differ substantially from practices in the Anglo-Saxon model. This article focuses on the German system in particular, in which universal banks are the primary source of corporate finance to firms of all sizes. 2 These …
Why Teaching Ethics to AI Practitioners Is Important

We argue that it is crucial to the future of AI that our students be trained in multiple complementary modes of ethical reasoning, so that they may make ethical design and implementation choices, ethical career decisions, and that their software will be programmed to take into account the complexities of acting ethically in the world.
Prevalence of atrial fibrillation and association of previous antithrombotic treatment in patients with cerebral microbleeds.

BACKGROUND AND PURPOSE
Cerebral microbleeds (CMBs) are associated with an increased risk of intracerebral hemorrhage. The impact of oral anticoagulation (OAC) on CMBs is not well characterized. Our aim was to assess the prevalence of CMBs in stroke and transient ischaemic attack (TIA) patients with atrial fibrillation (AF) and to analyze the implications of previous treatment with OAC.


METHODS
In this retrospective analysis on data from a prospectively recruiting stroke registry, patients with ischaemic stroke or TIA with brain magnetic resonance imaging including susceptibility weighted imaging were consecutively enrolled during a 3-year period. For each patient cardiovascular risk factors, AF history and recent diagnosis of AF, present use of OAC and antiplatelets, the National Institute of Health Stroke Scale and the premorbid modified Rankin Scale score were recorded. Two independent raters identified CMBs according to consensus criteria. CMB location was classified as lobar, deep or in the posterior fossa.


RESULTS
In all, 785 patients (mean age 63.9 ± 14.2 years) were included. At least one CMB was detected in 186 (23.7%) patients. CMBs were significantly more frequent in patients with AF (30.5% vs. 22.4%). Patients with previous OAC treatment were more likely to have CMBs (36.7% vs. 22.8%, P = 0.03) and abundant CMBs (n > 10) were more frequent in anticoagulated patients even after adjustment for age. However, age was the only independent factor predicting CMBs (P = 0.001).


CONCLUSIONS
Cerebral microbleeds are common in elderly AF patients with acute ischaemic stroke. Previous OAC is associated with a higher number of CMBs predominantly in the lobar location. Establishing a causal relationship requires prospective longitudinal investigation.
MOG-IgG in NMO and related disorders: a multicenter study of 50 patients. Part 3: Brainstem involvement - frequency, presentation and outcome

Myelin oligodendrocyte glycoprotein antibodies (MOG-IgG) are present in a subset of aquaporin-4 (AQP4)-IgG-negative patients with optic neuritis (ON) and/or myelitis. Little is known so far about brainstem involvement in MOG-IgG-positive patients. To investigate the frequency, clinical and paraclinical features, course, outcome, and prognostic implications of brainstem involvement in MOG-IgG-positive ON and/or myelitis. Retrospective case study. Among 50 patients with MOG-IgG-positive ON and/or myelitis, 15 (30 %) with a history of brainstem encephalitis were identified. All were negative for AQP4-IgG. Symptoms included respiratory insufficiency, intractable nausea and vomiting (INV), dysarthria, dysphagia, impaired cough reflex, oculomotor nerve palsy and diplopia, nystagmus, internuclear ophthalmoplegia (INO), facial nerve paresis, trigeminal hypesthesia/dysesthesia, vertigo, hearing loss, balance difficulties, and gait and limb ataxia; brainstem involvement was asymptomatic in three cases. Brainstem inflammation was already present at or very shortly after disease onset in 7/15 (47 %) patients. 16/21 (76.2 %) brainstem attacks were accompanied by acute myelitis and/or ON. Lesions were located in the pons (11/13), medulla oblongata (8/14), mesencephalon (cerebral peduncles; 2/14), and cerebellar peduncles (5/14), were adjacent to the fourth ventricle in 2/12, and periaqueductal in 1/12; some had concomitant diencephalic (2/13) or cerebellar lesions (1/14). MRI or laboratory signs of blood-brain barrier damage were present in 5/12. Cerebrospinal fluid pleocytosis was found in 11/14 cases, with neutrophils in 7/11 (3-34 % of all CSF white blood cells), and oligoclonal bands in 4/14. Attacks were preceded by acute infection or vaccination in 5/15 (33.3 %). A history of teratoma was noted in one case. The disease followed a relapsing course in 13/15 (87 %); the brainstem was involved more than once in 6. Immunosuppression was not always effective in preventing relapses. Interferon-beta was followed by new attacks in two patients. While one patient died from central hypoventilation, partial or complete recovery was achieved in the remainder following treatment with high-dose steroids and/or plasma exchange. Brainstem involvement was associated with a more aggressive general disease course (higher relapse rate, more myelitis attacks, more frequently supratentorial brain lesions, worse EDSS at last follow-up). Brainstem involvement is present in around one third of MOG-IgG-positive patients with ON and/or myelitis. Clinical manifestations are diverse and may include symptoms typically seen in AQP4-IgG-positive neuromyelitis optica, such as INV and respiratory insufficiency, or in multiple sclerosis, such as INO. As MOG-IgG-positive brainstem encephalitis may take a serious or even fatal course, particular attention should be paid to signs or symptoms of additional brainstem involvement in patients presenting with MOG-IgG-positive ON and/or myelitis.
Effects of pravastatin on mortality in patients with and without coronary heart disease across a broad range of cholesterol levels. The Prospective Pravastatin Pooling project.

AIMS
To assess the effects of pravastatin on all-cause mortality and cause-specific mortality and to compare the effects for patients with prior coronary heart disease with those for patients without, using pooled data from the Long-Term Intervention with Pravastatin in Ischaemic Disease (LIPID) study, the Cholesterol and Recurrent Events (CARE) study, and the West of Scotland Coronary Prevention Study (WOSCOPS).


METHODS AND RESULTS
13 173 patients with coronary heart disease and 6595 men with elevated cholesterol and no prior coronary disease received pravastatin, 40 mg daily, or placebo for an average of 5 to 6 years. Data were analysed according to a pre-specified, published protocol. For all three trials combined, the mortality among patients assigned pravastatin was significantly lower, at 7.9%, than the 9.8% among those assigned placebo, a relative risk reduction of 20% (95% confidence interval (CI) 12-27%, P<0.0001). Active treatment was associated with a reduction in coronary mortality (24%, 95% CI 14-33%). Larger reductions in absolute risk were estimated in those with prior coronary heart disease than in those without.


CONCLUSION
Treatment with pravastatin over 5 years reduces all-cause mortality and coronary mortality in patients with and those without a history of coronary heart disease. The size of the benefit was related principally to the baseline risk.
Validation of Omron HBP-1300 professional blood pressure monitor based on auscultation in children and adults

UNLABELLED
BACKGROUnD: To determine whether the professional Omron HBP-1300 blood pressure (BP) monitor meets American Association for the Advancement of Medical Instrumentation (AAMI) accuracy standards in Chinese children and adults.


METHOD
According to the AAMI protocol, simultaneous auscultatory measurements by two observers using a mercury manometer were obtained in participants using the Omron HBP-1300. Triple measurements were obtained after a minimum 5-min rest with a 1-min interval between adjacent measurements.


RESULTS
A total of 85 participants submitted to 255 doctor-measured BP and 255 successful professional monitor readings. The initial auscultation systolic BP was <100 mmHg in 25 participants (29.4%), 100-160 mmHg in 53 participants (62.4%), and >160 mmHg in seven participants (8.2%). All of the simultaneous measurements agreed to within ± 10 mmHg, while 95% agreed to within ± 4 mmHg for both systolic and diastolic BP, and the consistency between two observers was satisfactory. The difference between the devices was -1.3 ± 3.6 mmHg for systolic BP and 0.7 ± 3.8 mmHg for diastolic BP and by AAMI method 1, which met this guideline. The average difference between two devices by AAMI method 2 was 1.4 ± 3.2 mmHg for systolic BP and 1.0 ± 3.9 mmHg for diastolic BP, which met this guideline.


CONCLUSION
The professional BP monitor Omron HBP-1300 is desirable for measuring the BP for Chinese children and adults.
A Phase II Study of Sorafenib Combined With Cetuximab in EGFR-Expressing, KRAS-Mutated Metastatic Colorectal Cancer.

BACKGROUND
Mutations in the KRAS gene predict for resistance to anti-epidermal growth factor receptor (EGFR) therapies, including cetuximab. Upregulation of vascular endothelial growth factor (VEGF)-A has been implicated in resistance to anti-EGFR treatment. Abrogation of the VEGF and RAS/RAF/MEK/ERK pathways has the potential to restore cetuximab sensitivity.


PATIENTS AND METHODS
Adult patients with histologically documented, measurable, EGFR-expressing, KRAS-mutated metastatic colorectal cancer (mCRC) that had progressed after 5-fluorouracil-based regimens were treated with sorafenib 400 mg orally twice daily and intravenous cetuximab weekly in 28-day cycles. The primary endpoint was the response rate (complete response, partial response, and stable disease at 4 cycles). The secondary endpoints included plasma biomarker analysis of angiogenic cytokines and correlative imaging studies with dynamic contrast-enhanced magnetic resonance imaging and zirconium 89-panitumumab.


RESULTS
Of the 30 patients enrolled, 26 were evaluable for response. Of the 26 patients evaluated, 4 had stable disease at 4 cycles and 1 had stable disease at 8 cycles. The median progression-free survival was 1.84 months. The common toxicities were rash, diarrhea, and liver enzyme elevations. Of the angiogenic cytokines evaluated, only the placental growth factor increased significantly with treatment (P < .0001). No pharmacodynamic parameters were associated with the treatment response.


CONCLUSION
We report the results of a trial that combined cetuximab and sorafenib for the treatment of KRAS-mutated mCRC, with correlative imaging studies and pharmacodynamic angiogenic cytokine profiling as downstream markers of EGFR and VEGF receptor (VEGFR) signaling. No objective responses were observed. Additional development of biomarkers for patient selection is needed to evaluate combined EGFR and VEGFR blockade as a therapeutic option in KRAS-mutated CRC.
Uncovering the Influence of Game Components on Creativity

Especially in knowledge societies, creativity is becoming an ever more important trait. In order to uphold progress and innovation, it is essential to hoan this trait. Playing (video) games has been found to promote creative thinking. However, there is yet a lack of understanding regarding which processes within games cause this effect. In order to effectively use games to train or use as a catalyst for creative potential, it is of relevance to uncover the influence of individual game components. This research takes an approach in investigating the influence of game components on creativity tests. We conducted an online user study with four conditions (control, levels, scarcity and theme), where creativity was assessed as a construct of cognitive abilities. Our results show that the inclusion of individual game components impacted the creative performance of participants regarding fluency, originality and elaboration.
Drug resistance in HIV patients with virological failure or slow virological response to antiretroviral therapy in Ethiopia

BACKGROUND
The ongoing scale-up of antiretroviral therapy (ART) in sub-Saharan Africa has prompted the interest in surveillance of transmitted and acquired HIV drug resistance. Resistance data on virological failure and mutations in HIV infected populations initiating treatment in sub-Saharan Africa is sparse.


METHODS
HIV viral load (VL) and resistance mutations pre-ART and after 6 months were determined in a prospective cohort study of ART-naïve HIV patients initiating first-line therapy in Jimma, Ethiopia. VL measurements were done at baseline and after 3 and 6 months. Genotypic HIV drug resistance (HIVDR) was performed on patients exhibiting virological failure (>1000 copies/mL at 6 months) or slow virological response (>5000 copies/mL at 3 months and <1000 copies/mL at 6 months).


RESULTS
Two hundred sixty five patients had VL data available at baseline and at 6 months. Virological failure was observed among 14 (5.3%) participants out of 265 patients. Twelve samples were genotyped and six had HIV drug resistance (HIVDR) mutations at baseline. Among virological failures, 9/11 (81.8%) harbored one or more HIVDR mutations at 6 months. The most frequent mutations were K103N and M184VI.


CONCLUSIONS
Our data confirm that the currently recommended first-line ART regimen is efficient in the vast majority of individuals initiating therapy in Jimma, Ethiopia eight years after the introduction of ART. However, the documented occurrence of transmitted resistance and accumulation of acquired HIVDR mutations among failing patients justify increased vigilance by improving the availability and systematic use of VL testing to monitor ART response, and underlines the need for rapid, inexpensive tests to identify the most common drug resistance mutations.
Motion based video super resolution using edge directed interpolation and complex wavelet transform

This paper proposes a novel super resolution technique using dual tree complex wavelet transform (DT-CWT) and new edge directional interpolation (NEDI) based on localizing motion blocks in consecutive frames. A super resolution process is applied on the extracted motion blocks and the static region of the frame to generate the low frequency subbands of DT-CWT. DT-CWT decomposition followed by NEDI generates the high frequency subbands in order to obtain the components required for inverse DT-CWT (IDT-CWT). Finally, the super resolved output frame is generated by composing the obtained high and low frequency subbands using IDT-CWT. Experimental results based on PSNR measures illustrate the advantage of proposed technique over the state of the art video resolution enhancement methods. & 2013 Elsevier B.V. All rights reserved.