Miracle-dz/UniFAR-FTUs huggingface dataset:
A Dataset and a Technique for Generalized Nuclear Segmentation for Computational Pathology

Nuclear segmentation in digital microscopic tissue images can enable extraction of high-quality features for nuclear morphometrics and other analysis in computational pathology. Conventional image processing techniques, such as Otsu thresholding and watershed segmentation, do not work effectively on challenging cases, such as chromatin-sparse and crowded nuclei. In contrast, machine learning-based segmentation can generalize across various nuclear appearances. However, training machine learning algorithms requires data sets of images, in which a vast number of nuclei have been annotated. Publicly accessible and annotated data sets, along with widely agreed upon metrics to compare techniques, have catalyzed tremendous innovation and progress on other image classification problems, particularly in object recognition. Inspired by their success, we introduce a large publicly accessible data set of hematoxylin and eosin (H&E)-stained tissue images with more than 21000 painstakingly annotated nuclear boundaries, whose quality was validated by a medical doctor. Because our data set is taken from multiple hospitals and includes a diversity of nuclear appearances from several patients, disease states, and organs, techniques trained on it are likely to generalize well and work right out-of-the-box on other H&E-stained images. We also propose a new metric to evaluate nuclear segmentation results that penalizes object- and pixel-level errors in a unified manner, unlike previous metrics that penalize only one type of error. We also propose a segmentation technique based on deep learning that lays a special emphasis on identifying the nuclear boundaries, including those between the touching or overlapping nuclei, and works well on a diverse set of test images.
The Princess Marina Hospital accident and emergency triage scale provides highly reliable triage acuity ratings

Objective To determine the interrater reliability of triage acuity ratings by healthcare workers (HCW) using a previous triage system (PTS) and the Princess Marina Hospital accident and emergency centre triage scale (PATS), a local adaptation of the widely used and studied South African triage scale. Methods A cross-sectional study was performed on HCW in an emergency department (ED) in Botswana to determine the interrater reliability of triage acuity ratings when using PTS and PATS to assign triage categories to 25 written vignettes after PATS training. The intraclass correlation coefficient (ICC) was calculated to assess interrater reliability, and graphic displays were used to portray rating distributions for vignettes with a mean rating of different acuity categories for PTS and PATS. Results 44 HCW completed the scenarios. The ICC for the group of HCW was 0.52 (95% CI 0.37 to 0.67) using PTS and 0.87 (95% CI 0.80 to 0.93) using PATS. The ICC values were higher for PATS than PTS regardless of the number of years of experience of the HCW and the level of the HCW (specialist, medical officer, nurse, nurse aide). Graphic displays showed that there was less variability at all acuity levels when using PATS compared with PTS. Conclusion The reliability measures in this study indicate very high interrater agreement and limited variability in acuity ratings when using the PATS as opposed to moderate agreement and increased variability in acuity ratings when using PTS. This suggests that PATS is reliably applied by all levels of HCW and supports the feasibility of the further implementation of PATS in ED in Botswana and in other similar settings.
Simultaneous inference of a binary composite endpoint and its components

ABSTRACT Binary composite endpoints offer some advantages as a way to succinctly combine evidence from a number of related binary endpoints recorded in the same clinical trial into a single outcome. However, as some concerns about the clinical relevance as well as the interpretation of such composite endpoints have been raised, it is recommended to evaluate the composite endpoint jointly with the involved components. We propose an approach for carrying out simultaneous inference based on separate model fits for each endpoint, yet controlling the familywise type I error rate asymptotically. The key idea is to stack parameter estimates from the different fits and derive their joint asymptotic distribution. Simulations show that the proposed approach comes closer to nominal levels and has comparable or higher power as compared to existing approaches, even for moderate sample sizes (around 100-200 observations). The method is compared to the gatekeeping approach and results are provided in the Supplementary Material. In two data examples we show how the procedure may be adapted to handle local significance levels specified through a priori given weights.
Isoprostane generation and function.

Free radicals derived primarily from molecular oxygen have been implicated in a variety of human disorders including atherosclerosis, cancer, neurodegenerative diseases, and aging.1 Damage to tissue biomolecules, including lipids, proteins, and DNA, by free radicals is postulated to contribute importantly to the pathophysiology of oxidative stress. Lipids are readily attacked by free radicals resulting in the formation of a number of peroxidation products.2 The isoprostanes (IsoPs) are a unique series of prostaglandin-like compounds formed in vivo via the non-enzymatic free radical-initiated peroxidation of arachidonic acid, a ubiquitous polyunsaturated fatty acid (PUFA). Since discovery of these molecules over twenty years ago by Morrow and Roberts, one class of IsoPs, the F2-IsoPs, have become the biomarker of choice for assessing endogenous oxidative stress because these molecules are chemically stability and have been detected in all biological fluids and tissues analyzed.3-5 In addition to F2-IsoPs, a variety of IsoPs with different ring structures have been identified. Several of these compounds possess potent biological activities that could account for some of the pathophysiological effects of oxidative injury. Further, IsoP-like molecules are also generated from a number of different PUFAs including α-linolenic acid, eicosapentaenoic acid (EPA), adrenic acid, and docosahexaenoic acid (DHA) (Figure 1). There are many excellent reviews in the literature describing not only the quantification of F2-IsoPs in human health and disease but also the biological activities of these molecules.6-9 Thus, this review seeks to give readers a comprehensive, up-to-date overview of our current knowledge regarding IsoPs including the chemistry and biochemistry of their formation and metabolism, the utility of measuring these compounds as markers of in vivo oxidant stress, and their biological properties.
Leukocyte Antigen-related Protein Tyrosine Phosphatase Negatively Regulates Hydrogen Peroxide-induced Vascular Smooth Muscle Cell Apoptosis*

Reactive oxygen species (ROS) have been implicated in vascular smooth muscle cell (VSMC) apoptosis, a hallmark of advanced atherosclerotic lesions. Transient oxidation and inactivation of protein-tyrosine phosphatases play a critical role in cellular response to ROS production. However, the function of leukocyte antigen-related (LAR) protein-tyrosine phosphatase in ROS signaling is not known. To determine the expression of LAR in ROS-induced apoptosis, we investigated hydrogen peroxide-induced cell death and signaling in aortic VSMCs from wild-type and LAR-/- mice. Histone-associated DNA fragmentation and caspase-3/7 activity were significantly enhanced, mitochondrial membrane integrity was compromised, and cell viability was significantly decreased following H2O2 treatment in LAR-/- VSMCs compared with wild-type cells. Stronger and sustained increase in autophosphorylation and activity of Fyn, an Src family tyrosine kinase, was observed in LAR-/- cells compared with wild-type cells following H2O2 treatment. LAR binds to activated Fyn in H2O2-treated VSMCs, and recombinant LAR dephosphorylates phosphorylated-Fyn in vitro. In addition, LAR deficiency enhanced H2O2-induced phosphorylation of Janus kinase 2 (JAK2), signal transducer and activator of transcription 3 (STAT3), and p38 mitogen-activated protein kinase (MAPK). PP2, a Fyn-specific inhibitor, blocked JAK2, STAT3, and p38 MAPK activation and significantly attenuated apoptosis induced by H2O2. AG490, a JAK2-specific inhibitor, significantly attenuated H2O2-induced apoptosis, and blocked H2O2-induced activation of STAT3, but not p38 MAPK in both wild-type and LAR-/- VSMCs. Attenuation of Fyn expression by short hairpin RNA significantly decreased H2O2-induced downstream signaling and apoptosis in VSMCs. Together, these data indicate that LAR regulates Fyn/JAK2/STAT3 and Fyn/p38 MAPK pathways involved in ROS-induced apoptosis.
Stop talking and type: comparing virtual and face-to-face mentoring in an epistemic game

Research has shown that computer games and other virtual environments can support significant learning gains because they allow young people to explore complex concepts in simulated form. However, in complex problem-solving domains, complex thinking is learned not only by taking action, but also with the aid of mentors who provide guidance in the form of questions, instructions, advice, feedback and encouragement. In this study, we examine one context of such mentoring to understand the impact of replacing face-to-face interactions between mentors and students with virtual, chat-based interactions. We use pre- and post-measures of learning and a post-measure of engagement, as well as epistemic network analysis (ENA), a novel quantitative method, to examine student and mentor discourse. Our results suggest that mentoring via online chat can be as effective as mentoring face-to-face in appropriately structured contexts more generally – and that ENA may be a useful tool for assessing student and mentor discourse in the context of learning interactions.
ISLANDER: an electronic institutions editor

In this paper we present ISLANDER, a tool for the specification and verification of agent mediated electronic institutions.We have defined a textual declarative language for the specification of the components of an institution. Also an ISLANDER editor is presented. It facilitates the work of the institution designer permitting the combination of graphical and textual specifications. We take the stance that a verifiable formal specification is needed before starting the development of complex systems. This tool is our first step towards having a framework for the design and development of infrastructures for open multi-agent systems.
Potential Role of Fosfomycin in the Treatment of Community-Acquired Lower Urinary Tract Infections Caused by Extended-Spectrum &bgr;-Lactamase-Producing Escherichia coli

Extended-spectrum &bgr;-lactamase-producing Escherichia coli (ESBLEC) are emerging pathogens causing urinary tract infections (UTIs) in community patients worldwide. Treatment for community-acquired ESBLEC UTIs, especially in the outpatient setting, may be problematic because many of the strains are resistant to the traditional oral therapies. Fosfomycin is an oral agent that is approved for the treatment of uncomplicated UTIs caused by Enterococcus faecalis and E. coli. Data evaluating the clinical efficacy of fosfomycin for the treatment of community-acquired ESBLEC lower UTIs are limited. Three studies evaluating fosfomycin in the treatment of ESBLEC lower UTIs have been conducted. Clinical success was documented in >78% of patients. From the available data, it seems that fosfomycin may be an effective and reasonable treatment option for outpatient management of community-acquired ESBLEC UTIs, excluding pyelonephritis. Fosfomycin is a very attractive agent because it is available orally, has limited drug interactions, has a favorable adverse event profile, and would be very cost effective considering the potential complications of inadequate treatment and the high cost associated with parenteral therapies. Limitations to the clinical use of fosfomycin may include optimal dose and duration not being established, fosfomycin not often being included on culture and sensitivity reports and emerging resistance.
Geminate Devoicing in Japanese Loanwords: Theoretical and Experimental Investigations

This paper provides an overview of theoretical and experimental investigations into voiced geminates in Japanese. Active discussion was initiated by Nishimura's (2003) discovery that in Japanese loanword phonology, voiced geminates can be devoiced, when they co-occur with another voiced obstruent (e.g. /doggu/ /dokku/ ‘dog’). This context-sensitive devoicing of geminates has been analyzed within several different theoretical frameworks. The phonetic and psycholinguistic natures of voiced geminates have also been explored, in tandem with corpus-based analyses and computational modeling. This devoicing pattern of voiced geminates in Japanese therefore has had substantial impacts on the recent phonological literature. The empirical focus of this paper is on one simple devoicing phenomenon in Japanese, but implications for general linguistic theories are discussed throughout the paper.
Doppler lidar measurements of oriented planar ice crystals falling from supercooled and glaciated layer clouds

The properties of planar ice crystals settling horizontally have been investigated using a vertically pointing Doppler lidar. Strong specular reflections were observed from their oriented basal facets, identified by comparison with a second lidar pointing 4° from zenith. Analysis of 17 months of continuous high‐resolution observations reveals that these pristine crystals are frequently observed in ice falling from mid‐level mixed‐phase layer clouds (85% of the time for layers at −15 °C). Detailed analysis of a case study indicates that the crystals are nucleated and grow rapidly within the supercooled layer, then fall out, forming well‐defined layers of specular reflection. From the lidar alone the fraction of oriented crystals cannot be quantified, but polarimetric radar measurements confirmed that a substantial fraction of the crystal population was well oriented. As the crystals fall into subsaturated air, specular reflection is observed to switch off as the crystal faces become rounded and lose their faceted structure.
Clinical Characteristics, Biological Profile, and Outcome of Biphenotypic Acute Leukemia: A Case Series

Background: Biphenotypic acute leukemia (BAL) is a rare type of acute leukemia that presents with a high degree of heterogeneity and is not well defined. Methods: We identified 51 cases (3%) of BAL from 1,693 newly diagnosed acute leukemia patients according to the EGIL scoring system. The immunophenotyping, cytogenetics, treatment, and outcome of 39 BAL patients were retrospectively analyzed. Results: There were 23 (59%) cases of the myeloid and B-lymphoid phenotype, 14 (36%) cases of the myeloid and T-lymphoid phenotype, and 1 case (3%) of the trilineage phenotype or B/T phenotype. Abnormal karyotypes were detected in 76% of the 37 validated patients and displayed a high degree of heterogeneity. Combined regimens for both acute myeloid leukemia (AML) and acute lymphoid leukemia (ALL), as well as ALL type regimens, appeared to achieve a better complete remission rate than AML type regimens (71 and 64 vs. 33%, respectively). BAL patients with complex karyotypes or a rearrangement of chromosome 11 had a significantly reduced survival rate in comparison to patients with normal, t(8; 21), or t(9; 22) karyotypes. The probability of overall survival and disease-free survival at 2 years was 26 and 18%, respectively. Conclusions: Our findings indicate that BAL shows a high incidence of abnormal karyotypes and a poor prognosis. Combined-type regimens or ALL-based protocols are effective for the treatment of BAL.
Effectiveness of Teacher-Child Interaction Training (TCIT) in a Preschool Setting

This research addressed the need for trained child care staff to support optimal early social-emotional development in urban, low-income, ethnic minority children. We evaluated effectiveness of Teacher-Child Interaction Training (TCIT), an approach adapted from Eyberg’s Parent-Child Interaction Therapy (PCIT). TCIT focuses on increasing preschool teachers’ positive attention skills and consistent discipline in order to enhance children’s psychosocial functioning and prevent mental health problems. A total of 12 teachers participated in small-group workshop sessions with in vivo coaching on their use of skills in the classroom. A multiple-baseline design across four classrooms (3 teachers each) evaluated effects of training on teacher behaviors during weekly classroom observations. Findings indicated systematic increases in trained skills during intervention, and consumer evaluations showed that the training was rated positively. Our results suggest that TCIT is a promising approach for enhancing positive teacher-child interactions in a preschool setting and should receive further investigation.
A survey on health literacy of inpatient's educational hospitals of Isfahan University of Medical Sciences in 2012

Background: Health literacy is an individual's need in each Society. Health literacy is a set of skills in reading, listening, analysis, decision making and the ability to apply these skills to health situations. The purpose of this study was to assess health literacy level in Inpatients of educational Hospitals of Isfahan University of Medical Sciences in 2012. Materials and Methods: A navigational and analytical- applied survey of 384 Inpatients was conducted in educational hospitals of Isfahan University of Medical Sciences. Health literacy was measured by the Test of Functional Health Literacy in Adults (TOFHLA). Reliability of Questionnaire was obtained through Cronbach's alpha and it was 0/89 and its validity was confirmed by experts. The data were collected in clinical inquiry and were analyzed using SPSS (as Descriptive was Frequency distribution, mean, standard deviation and as analytical was Independent T-test, ANOVA and Pearson correlation test and Spearman correlation test). Findings: Results showed that the average of Health literacy scores in Inpatients was 35/31 in Numeracy test and 31/94 in Reading Comprehension test. The mean total score of health literacy was 29/63. Thus, the Most of these Inpatients were found to have inadequate health literacy. No significant association was found between health literacy level and gender, income, Occupation and residence. Health literacy was associated with age, marriage status and education. Conclusion: The results showed that most of Inpatients in of educational Hospitals of Isfahan University of Medical Sciences were marginal and inadequate health literacy. Therefore, they need to more help and details to understand and use health information.
Improving placement algorithms by using visualization tools

EDA tools paved the way for the integration of billion of components in a single integrated circuit. However, many tools still rely on text interfaces. The use of visualizations tools can help not only to provide a visual output of an EDA tool but also to show how a tool is performing in terms of quality of results. A good graphic output can be useful to improve algorithms or develop new ones. Some placement visualization tools are shown and it is provided a perspective how these visualization tools contributed to the improvement and development of new algorithms developed by us.
Moral Property Rights in Bargaining with Infeasible Claims

In many business transactions, labor-management relations, international conflicts, and welfare-state reforms, bargainers hold strong entitlements that are often generated by claims that are not feasible anymore. These entitlements seem to shape negotiation behavior considerably. By using the novel setup of a "bargaining with claims" experiment, we provide new systematic evidence tracking the influence of entitlements and obligations through the whole bargaining process. We find strong entitlement effects that shape opening offers, bargaining duration, concessions, and (dis)agreements. We argue that entitlements constitute a "moral property right" that is influential independent of negotiators' legal property rights.
Associations among Circulating Sex Hormones, Insulin-Like Growth Factor, Lipids, and Mammographic Density in Postmenopausal Women

Objective: Hormone therapy use has been positively associated with mammographic density in several studies. However, few studies have examined the association between endogenous hormone levels and mammographic density. Therefore, we evaluated the relationship of endogenous sex hormones, insulin-like growth factor (IGF), and lipids with mammographic density in 88 overweight, postmenopausal women not taking hormone therapy. Methods: Percent density and dense area were evaluated as continuous measures using a computer-assisted program. We used multiple linear regression to evaluate the associations of sex hormones, IGF, and cholesterol with mammographic density, adjusting for confounders, including adiposity. We evaluated stratification by history of hormone therapy use (former versus never) and hormone therapy latency (<5 versus ≥5 years). Results: Among former hormone therapy users, mammographic density was inversely associated with circulating levels of estrone (P = 0.01), estradiol (P = 0.003), free estradiol (P = 0.004), testosterone (P = 0.04), free testosterone (P = 0.02), androstenedione (P < 0.001), dehydroepiandrosterone (P = 0.01), and the ratio of IGF-I to its binding protein (IGF-I/IGFBP-3; P = 0.04). We found similar associations when we limited the analyses to women who had used hormone therapy within the past 5 years. We also noted positive associations of mammographic density with total cholesterol (P = 0.03) and low-density lipoprotein (P = 0.03) among former hormone therapy users. No associations were noted among women who had never used hormone therapy. Conclusions: These results suggest that there is an inverse relationship between endogenous sex hormones and mammographic density in postmenopausal women among former users of hormone therapy. This is not consistent with the hormone therapy literature and should be confirmed in larger studies.
Detection of four human coronaviruses in respiratory infections in children: A one‐year study in Colorado

Lower respiratory tract infections are the leading cause of death in children worldwide. Studies on the epidemiology and clinical associations of the four human non‐SARS human coronaviruses (HCoVs) using sensitive polymerase chain reaction (PCR) assays are needed to evaluate the clinical significance of HCoV infections worldwide. Pediatric respiratory specimens (1,683) submitted to a diagnostic virology laboratory over a 1‐year period (December 2004–November 2005) that were negative for seven respiratory viruses by conventional methods were tested for RNA of four HCoVs using sensitive RT‐PCR assays. Coronavirus RNAs were detected in 84 (5.0%) specimens: HCoV‐NL63 in 37 specimens, HCoV‐OC43 in 34, HCoV‐229E in 11, and HCoV‐HKU1 in 2. The majority of HCoV infections occurred during winter months, and over 62% were in previously healthy children. Twenty‐six (41%) coronavirus positive patients had evidence of a lower respiratory tract infection (LRTI), 17 (26%) presented with vomiting and/or diarrhea, and 5 (8%) presented with meningoencephalitis or seizures. Respiratory specimens from one immunocompromised patient were persistently positive for HCoV‐229E RNA for 3 months. HCoV‐NL63‐positive patients were nearly twice as likely to be hospitalized (P = 0.02) and to have a LRTI (P = 0.04) than HCoV‐OC43‐positive patients. HCoVs are associated with a small, but significant number (at least 2.4% of total samples submitted), of both upper and lower respiratory tract illnesses in children in Colorado. Our data raise the possibility that HCoV may play a role in gastrointestinal and CNS disease. Additional studies are needed to investigate the potential roles of HCoVs in these diseases. J. Med. Virol. 81:1597–1604, 2009. © 2009 Wiley‐Liss, Inc.