Miracle-dz/UniFAR-FTUs huggingface dataset:
Improved Methods to Generate Spheroid Cultures from Tumor Cells, Tumor Cells & Fibroblasts or Tumor-Fragments: Microenvironment, Microvesicles and MiRNA

Diagnostic and prognostic indicators are key components to achieve the goal of personalized cancer therapy. Two distinct approaches to this goal include predicting response by genetic analysis and direct testing of possible therapies using cultures derived from biopsy specimens. Optimally, the latter method requires a rapid assessment, but growing xenograft tumors or developing patient-derived cell lines can involve a great deal of time and expense. Furthermore, tumor cells have much different responses when grown in 2D versus 3D tissue environments. Using a modification of existing methods, we show that it is possible to make tumor-fragment (TF) spheroids in only 2–3 days. TF spheroids appear to closely model characteristics of the original tumor and may be used to assess critical therapy-modulating features of the microenvironment such as hypoxia. A similar method allows the reproducible development of spheroids from mixed tumor cells and fibroblasts (mixed-cell spheroids). Prior literature reports have shown highly variable development and properties of mixed-cell spheroids and this has hampered the detailed study of how individual tumor-cell components interact. In this study, we illustrate this approach and describe similarities and differences using two tumor models (U87 glioma and SQ20B squamous-cell carcinoma) with supporting data from additional cell lines. We show that U87 and SQ20B spheroids predict a key microenvironmental factor in tumors (hypoxia) and that SQ20B cells and spheroids generate similar numbers of microvesicles. We also present pilot data for miRNA expression under conditions of cells, tumors, and TF spheroids.
International differences in understanding recovery: systematic review

Aims. Mental health policy internationally varies in its support for recovery. The aims of this study were to validate an existing conceptual framework and then characterise by country the distribution, scientific foundations and emphasis in published recovery conceptualisations. Methods. Update and modification of a previously published systematic review and narrative synthesis of recovery conceptualisations published in English. Results. A total of 7431 studies were identified and 429 full papers reviewed, from which 105 conceptualisations in 115 papers were included and quality assessed using established rating scales. Recovery conceptualisations were identified from 11 individual countries, with 95 (91%) published in English-speaking countries, primarily the USA (47%) and the UK (25%). The scientific foundation was primarily qualitative research (53%), non-systematic literature reviews (24%) and position papers (12%). The conceptual framework was validated with the 18 new papers. Across the different countries, there was a relatively similar distribution of codings for each of five key recovery processes. Conclusions. Recovery as currently conceptualised in English-language publications is primarily based on qualitative studies and position papers from English-speaking countries. The conceptual framework was valid, but the development of recovery conceptualisations using a broader range of research designs within other cultures and non-majority populations is a research priority.
TRANSMISSION RATES AND THE EVOLUTION OF PATHOGENICITY

A propos de la relation entre taux de transmission et pouvoir pathogene dans l'evolution des systemes hote-parasite. Reprise des donnees empiriques de Fenner et Ratcliffe (1965) suite a l'introduction du virus du myxome chez des lapins en Australie, traitees par Anderson et May (1982, 1983), et du travail de Mead-Briggs et Vaughan (1975) considerant le pourcentage moyen de puces infectees a partir de lapins infectes par diverses souches du virus. Etude mathematique. Commentaires
Programming languages for distributed computing systems

When distributed systems first appeared, they were programmed in traditional sequential languages, usually with the addition of a few library procedures for sending and receiving messages. As distributed applications became more commonplace and more sophisticated, this ad hoc approach became less satisfactory. Researchers all over the world began designing new programming languages specifically for implementing distributed applications. These languages and their history, their underlying principles, their design, and their use are the subject of this paper. We begin by giving our view of what a distributed system is, illustrating with examples to avoid confusion on this important and controversial point. We then describe the three main characteristics that distinguish distributed programming languages from traditional sequential languages, namely, how they deal with parallelism, communication, and partial failures. Finally, we discuss 15 representative distributed languages to give the flavor of each. These examples include languages based on message passing, rendezvous, remote procedure call, objects, and atomic transactions, as well as functional languages, logic languages, and distributed data structure languages. The paper concludes with a comprehensive bibliography listing over 200 papers on nearly 100 distributed programming languages.
The Mediterranean Diet: its definition and evaluation of a priori dietary indexes in primary cardiovascular prevention

Abstract We have analysed the definition of Mediterranean Diet in 28 studies included in six meta-analyses evaluating the relation between the Mediterranean Diet and primary prevention of cardiovascular disease. Some typical food of this dietary pattern like whole cereals, olive oil and red wine were taken into account only in a few a priori indexes, and the dietary pattern defined as Mediterranean showed many differences among the studies and compared to traditional Mediterranean Diet of the early 1960s. Altogether, the analysed studies show a protective effect of the Mediterranean Diet against cardiovascular disease but present different effects against specific conditions as cerebrovascular disease and coronary heart disease. These different effects might depend on the definition of Mediterranean Diet and the indexes of the adhesion to the same one used. To compare the effects of the Mediterranean Diet against cardiovascular disease, coronary heart disease and stroke a univocal model of Mediterranean Diet should be established as a reference, and it might be represented by the Modern Mediterranean Diet Pyramid. The a priori index to evaluate the adhesion to Mediterranean Diet might be the Mediterranean-Style Dietary Pattern Score that has some advantages in comparison to the others a priori indexes.
Sex steroid modulation of gonadotropins in normal men and in androgen insensitivity syndrome.

Abstract The respective roles of androgens and estrogens in the modulation of LH and FSH secretion in men have not been clearly defined. In this study, we compared gonadotropins basally and after stimulation with gonadotropin-releasing hormone in four states characterized by different sensitivity to sex steroids: 1) in five normal men (intact sensitivity to both androgens and estrogens), 2) in two patients with complete androgen insensitivity syndrome (AIS; selective androgen insensitivity), 3) in normal men treated with clomiphene citrate (selective estrogen insensitivity), and 4) in AIS patients treated with clomiphene (combined androgen and estrogen insensitivity). Basal LH levels were increased in selective androgen and selective estrogen insensitivities; LH levels were elevated further in combined androgen and estrogen insensitivities. The elevated LH levels in AIS were suppressible by exogenous administration of estradiol benzoate. Basal FSH was not increased in selective androgen insensitivity, but.
Analysis of multistress-accelerated aged stator bars using a three-phase test arrangement

The aging characteristics of stator bars, which have been subjected to accelerated aging tests in a three-phase model stator under simultaneously applied electrical, mechanical, and thermal stresses, have been evaluated using diagnostic test procedures. The ac breakdown test has been found to be the most effective means for assessing the extent of aging undergone by the stator bars. The results indicate that under multistress conditions relatively small increases in the magnitudes of the stress acceleration factors are sufficient to lead to significant increases in the aging rate of the insulating systems of stator bars.
Predicting Re-opened Bugs: A Case Study on the Eclipse Project

Bug fixing accounts for a large amount of the software maintenance resources. Generally, bugs are reported, fixed, verified and closed. However, in some cases bugs have to be re-opened. Re-opened bugs increase maintenance costs, degrade the overall user-perceived quality of the software and lead to unnecessary rework by busy practitioners. In this paper, we study and predict re-opened bugs through a case study on the Eclipse project. We structure our study along 4 dimensions: 1) the work habits dimension (e.g., the weekday on which the bug was initially closed on), 2) the bug report dimension (e.g., the component in which the bug was found) 3) the bug fix dimension (e.g., the amount of time it took to perform the initial fix) and 4) the team dimension (e.g., the experience of the bug fixer). Our case study on the Eclipse Platform 3.0 project shows that the comment and description text, the time it took to fix the bug, and the component the bug was found in are the most important factors in determining whether a bug will be re-opened. Based on these dimensions we create decision trees that predict whether a bug will be re-opened after its closure. Using a combination of our dimensions, we can build explainable prediction models that can achieve 62.9% precision and 84.5% recall when predicting whether a bug will be re-opened.
Flexible Implementation of a WCDMA Rake Receiver

This paper presents an ASIC implementation of a WCDMA Rake receiver targeted for mobile terminals. The implementation is based on a FlexRake architecture that shares hardware resources between multipath components and uses data-level parallelism for despreading multiple code channels. This approach facilitates the flexibility of multipath operation and improves the receiver hardware efficiency. The architecture was implemented using register-transfer-level VHDL description and logic synthesis with standard cells. Synthesis for 0.18 μm CMOS technology resulted in 0.238 mm2 area and 45.5 μW power consumption at 1.6 V.
Caring for justice

Over the past decade, mainstream feminist theory has repeatedly and urgently cautioned against arguments which assert the existence of fundamental--or essential--differences between men and women. Any biological or natural differences between the sexes are often flatly denied, on the grounds that such an acknowledgment will impede women's claims to equal treatment. In Caring for Justice, Robin West turns her sensitive, measured eye to the consequences of this widespread refusal to consider how women's lived experiences and perspectives may differ from those of men. Her work calls attention to two critical areas in which an inadequate recognition of women's distinctive experiences has failed jurisprudence. We are in desperate need, she contends, both of a theory of justice which incorporates women's distinctive moral voice on the meaning of justice into our discourse, and of a theory of harm which better acknowledges, compensates, and seeks to prevent the various harms which women, disproportionately and distinctively, suffer. Providing a fresh feminist perspective on traditional jurisprudence, West examines such issues as the nature of justice, the concept of harm, economic theories of value, and the utility of constitutional discourse. She illuminates the adverse repercussions of the anti-essentialist position for jurisprudence, and offers strategies for correcting them. Far from espousing a return to essentialism, West argues an anti- anti-essentialism, which greatly refines our understanding of the similarities and differences between women and men.
Immunohistochemical expression of RANKL, RANK, and OPG in human oral squamous cell carcinoma.

BACKGROUND The mechanism of oral squamous cell carcinoma (SCC) invading jawbone remains controversial. Interactions between receptor activator of NF-kappaB (RANK) and its ligand (RANKL) are required for osteoclastogenesis. The binding of RANK and RANKL induces differentiation of osteoclasts, leading to bony destruction. Osteoprotegerin (OPG), a decoy receptor for RANKL, also binds to RANKL by competing with RANK, and this could protect against osseous destruction. MATERIALS AND METHODS Immunoexpression of RANKL, RANK, and OPG in 25 cases of human buccal SCCs without bony invasion and 15 cases of gingival SCCs with mandibular bony invasion was investigated. Normal oral mucosa from five individuals without betel-quid chewing or cigarette smoking was used as a control. The scores are designated as percentage of positive staining x intensity of staining for each section. RESULTS Strong cytoplasmic staining of RANKL proteins is detected in cancer cells of both buccal and gingival SCCs. The same protein is identified in cytoplasm of osteoclasts for all cases involving bony invasion. Strong cytoplasmic staining of RANKL is confined to basal layer for all normal mucosa. A similar staining pattern is noted for RANK protein in all buccal and gingival SCCs. An absence of staining of RANK protein is noted for all normal tissues. Weak to negative cytoplasmic stained OPG protein is present in all buccal and gingival SCCs, but is absent in all normal tissues. CONCLUSION These findings suggest the potential value of the RANK/RANKL/OPG pathway as biomarkers in human oral SCCs.
The effect of domiciliary noninvasive ventilation on clinical outcomes in stable and recently hospitalized patients with COPD: a systematic review and meta-analysis

Introduction Noninvasive ventilation (NIV) improves survival among patients with hypercapnic respiratory failure in hospital, but evidence for its use in domiciliary settings is limited. A patient’s underlying risk of having an exacerbation may affect any potential benefit that can be gained from domiciliary NIV. This is the first comprehensive systematic review to stratify patients based on a proxy for exacerbation risk: patients in a stable state and those immediately post-exacerbation hospitalization. Methods A systematic review of nonrandomized and randomized controlled trials (RCTs) was undertaken in order to compare the relative effectiveness of different types of domiciliary NIV and usual care on hospital admissions, mortality, and health-related quality of life. Standard systematic review methods were used for identifying studies (until September 2014), quality appraisal, and synthesis. Data were presented in forest plots and pooled where appropriate using random-effects meta-analysis. Results Thirty-one studies were included. For stable patients, there was no evidence of a survival benefit from NIV (relative risk [RR] 0.88 [0.55, 1.43], I2=60.4%, n=7 RCTs), but there was a possible trend toward fewer hospitalizations (weighted mean difference −0.46 [−1.02, 0.09], I2=59.2%, n=5 RCTs) and improved health-related quality of life. For posthospital patients, survival benefit could not be demonstrated within the three RCTs (RR 0.89 [0.53, 1.49], I2=25.1%), although there was evidence of benefit from four non-RCTs (RR 0.45 [0.32, 0.65], I2=0%). Effects on hospitalizations were inconsistent. Post hoc analyses suggested that NIV-related improvements in hypercapnia were associated with reduced hospital admissions across both populations. Little data were available comparing different types of NIV. Conclusion The effectiveness of domiciliary NIV remains uncertain; however, some patients may benefit. Further research is required to identify these patients and to explore the relevance of improvements in hypercapnia in influencing clinical outcomes. Optimum time points for commencing domiciliary NIV and equipment settings need to be established.
How Quickly Do Firms Adjust to Target Levels of Tax Avoidance

Prior research that examines firms’ tax avoidance activities focuses on the determinants of tax avoidance. Because a firm’s tax environment is constantly evolving, studying how quickly firms adjust their tax avoidance activities is necessary to develop a better understanding of the tradeoffs managers face to achieve a given level of tax avoidance. We test for evidence of targeting behavior by managers. Our results suggest that firms do have target levels of tax avoidance and that the typical firm converges towards its target at a rate of almost 69 percent over a three-year period. We also find that the speed of adjustment varies with a firm’s growth potential, presence of foreign operations, and governance. We appreciate helpful comments from John Campbell, Katherine Drake, Nancy Du, Nathan Goldman, Jeff Gramlich, Dave Guenther, Russ Hamilton, Shane Heitzman, Paul Hribar, John Jiang, Ed Outslay, Santhosh Ramalingegowda, Casey Schwab, James Stekelberg, Bridget Stomberg, Erin Towery, Brian Williams, Julie Xiao, and workshop participants at the UBCOW conference, Michigan State University, the University of Arizona, the University of Georgia, the University of Oregon, and Washington State University.
Assessment of activities performed by clinical nurse practitioners and implications for staffing and patient care at primary health care level in South Africa

Background The shortage of nurses in public healthcare facilities in South Africa is well documented; finding creative solutions to this problem remains a priority. Objective This study sought to establish the amount of time that clinical nurse practitioners (CNPs) in one district of the Western Cape spend on clinical services and the implications for staffing and skills mix in order to deliver quality patient care. Methods A descriptive cross-sectional study was conducted across 15 purposively selected clinics providing primary health services in 5 sub-districts. The frequency of activities and time CNPs spent on each activity in fixed and mobile clinics were recorded. Time spent on activities and health facility staff profiles were correlated and predictors of the total time spent by CNPs with patients were identified. Results The time spent on clinical activities was associated with the number of CNPs in the facilities. CNPs in fixed clinics spent a median time of about 13 minutes with each patient whereas CNPs in mobile clinics spent 3 minutes. Fixed-clinic CNPs also spent more time on their non-core functions than their core functions, more time with patients, and saw fewer patients compared to mobile-clinic CNPs. Conclusions The findings give insight into the time CNPs in rural fixed and mobile clinics spend with their patients, and how patient caseload may affect consultation times. Two promising strategies were identified – task shifting and adjustments in health worker deployment – as ways to address staffing and skills mix, which skills mix creates the potential for using healthcare workers fully whilst enhancing the long-term health of these rural communities.
Validation of the Rotterdam MOVE2PC Questionnaire for assessment of nurses' knowledge and opinions on palliative care.

The purpose of this study was the psychometric testing of a questionnaire to assess nurses' opinions, subjective norms, perceived difficulties, and knowledge related to palliative care. The 63-item MOVE2PC Questionnaire was tested among 219 nurses in groups differing in education and experience. The intra-rater agreement was moderate to good (к > .5κmax ), and internal consistency was good (alpha = .77). Construct validity was demonstrated by between-groups differences in knowledge, opinions, and perceived difficulties. Responsiveness was shown by improved scores after an education program. Time of completion was 20 minutes, and 99% skipped at most five items, demonstrating feasibility. Findings support the usefulness of the instrument for assessing nurses' knowledge and views on palliative care.
Alteration in the Expression of Cytochrome P450s (CYP1A1, CYP2E1, and CYP3A11) in the Liver of Mouse Induced by Microcystin-LR

Microcystins (MCs) are cyclic heptapeptide toxins and can accumulate in the liver. Cytochrome P450s (CYPs) play an important role in the biotransformation of endogenous substances and xenobiotics in animals. It is unclear if the CYPs are affected by MCs exposure. The objective of this study was to evaluate the effects of microcystin-LR (MCLR) on cytochrome P450 isozymes (CYP1A1, CYP2E1, and CYP3A11) at mRNA level, protein content, and enzyme activity in the liver of mice the received daily, intraperitoneally, 2, 4, and 8 µg/kg body weight of MCLR for seven days. The result showed that MCLR significantly decreased ethoxyresorufin-O-deethylase (EROD) (CYP1A1) and erythromycin N-demthylase (ERND) (CYP3A11) activities and increased aniline hydroxylase (ANH) activity (CYP2E1) in the liver of mice during the period of exposure. Our findings suggest that MCLR exposure may disrupt the function of CYPs in liver, which may be partly attributed to the toxicity of MCLR in mice.
X-Ray Spectral Variability of PKS 2005–489 During the Spectacular 1998 November Flare

We report on monitoring of the BL Lac object PKS 2005-489 by the Rossi X-Ray Timing Explorer (RXTE) in 1998 October-December. During these months, the source underwent a spectacular flare; at its peak on November 10, its 2-10 keV flux was 3.33 × 10-10 ergs cm-2 s-1, over 30 times brighter than in quiescence. During the rising phase, the X-ray spectrum of PKS 2005-489 hardened considerably, reaching α = 1.32 (Fν ∝ ν-α) near maximum. During the declining phase, the X-ray spectrum steepened rapidly, reaching α = 1.82, then became somewhat harder toward the end of December (α ~ 1.6). While such behavior has been seen before, the simplicity, magnitude, and duration of this flare allowed us to study it in great detail. We argue that this flare was caused by either the injection of particles into the jet or in situ particle acceleration and that the spectral steepening which followed the flare maximum was the result of synchrotron cooling. Contrary to other recently observed blazar flares (e.g., Mrk 501, 3C 279, PKS 2155-304), our results do not imply a major shift in the location of the synchrotron peak during this flare.
Acute Poisoning with a Glyphosate-Surfactant Herbicide ('Roundup'): A Review of 93 Cases

Between 1 January 1980, and 30 September 1989, 93 cases of exposure to herbicides containing glyphosphate and surfactant ('Roundup') were treated at Changhua Christian Hospital. The average amount of the 41% solution of glyphosate herbicide ingested by non-survivors was 184 ± 70 ml (range 85-200 ml), but much larger amounts (500 ml) were reported to have been ingested by some patients and only resulted in mild to moderate symptomatology. Accidental exposure was asymptomatic after dermal contact with spray (six cases), while mild oral discomfort occurred after accidental ingestion (13 cases). Intentional ingestion (80 cases) resulted in erosion of the gastrointestinal tract (66%), seen as sore throat (43%), dysphagia (31%), and gastrointestinal haemorrhage (8%). Other organs were affected less often (non-specific leucocytosis 65%, lung 23%, liver 19%, cardiovascular 18%, kidney 14%, and CNS 12%). There were seven deaths, all of which occurred within hours of ingestion, two before the patient arrived at the hospital. Deaths following ingestion of 'Roundup' alone were due to a syndrome that involved hypotension, unresponsive to intravenous fluids or vasopressor drugs, and sometimes pulmonary oedema, in the presence of normal central venous pressure.