Miracle-dz/UniFAR-FTUs huggingface dataset:
Hypertrophic cardiomyopathy genetic test reports: A qualitative study of patient understanding of uninformative genetic test results

Studies have shown that patients with hypertrophic cardiomyopathy (HCM) may misinterpret the meaning of uninformative genetic testing results to mean that a genetic etiology and family members’ risk is ruled out. We hypothesized that poor comprehension of the laboratory genetic test report may contribute to this misunderstanding. We conducted a qualitative study to examine patient understanding of uninformative laboratory results and reports and elicit suggestions for an improved report. Fifteen participants with HCM were interviewed after undergoing genetic testing and receiving their report. While all patients read the report, most participants reported only partially reading it. Most reported not understanding the report at all or only partially understanding it because a provider explained it to them. Some participants said that the report was helpful for understanding their result, but there was evidence of misunderstanding; most participants stated that specific aspects of the report were unhelpful. While most of our participants communicated risk with relatives, none said that the report helped with the communication. Most participants did not recall or find the accompanying physician‐directed result letter useful for their understanding or familial communication. Many participants expressed need for a supplemental report that illustrates a personalized clinical ‘action plan’ that could summarize clinical and familial implications of the result for the patient and their family. We conclude that laboratory reports and physician‐directed result letters did not help participants understand their results or their familial implications. Our results suggest opportunities for research to explore the utility of a patient‐directed result supplement to improve patient comprehension of genetic test results and outline clinical recommendations via a patient action plan.
BRASSINOSTEROID-INSENSITIVE2 Negatively Regulates the Stability of Transcription Factor ICE1 in Response to Cold Stress in Arabidopsis

The protein kinase BIN2 interacts with and phosphorylates INDUCER OF CBF EXPRESSION1 under cold stress, accelerating its proteasome-mediated degradation to negatively regulate freezing tolerance. Cold acclimation is a crucial strategy for plant survival at freezing temperatures. C-REPEAT BINDING FACTOR (CBF) genes are rapidly and transiently induced by low temperature and play important roles in cold acclimation. However, the mechanism underlying the attenuation of CBF expression during the later stages of the cold stress response is obscure. Here, we show that the protein kinase BRASSINOSTEROID-INSENSITIVE2 (BIN2) interacts with and phosphorylates INDUCER OF CBF EXPRESSION1 (ICE1) in Arabidopsis (Arabidopsis thaliana) under prolonged cold stress, facilitating the interaction between ICE1 and the E3 ubiquitin ligase HIGH EXPRESSION OF OSMOTICALLY RESPONSIVE GENE1 and thereby promoting ICE1 degradation. The kinase activity of BIN2 is inhibited during the early stages of the cold stress response and is subsequently restored, suggesting that BIN2 mainly downregulates ICE1 abundance when CBF expression is attenuated. A loss-of-function mutation of ICE1 partially suppresses the cold-induced expression of CBFs and compromises the enhanced freezing tolerance of bin2-3 bil1 bil2. These findings reveal an important role for BIN2 in fine-tuning CBF expression, and thus in balancing plant growth and the cold stress response.
The Conditional Distribution of Waiting Time Given Queue Length

Abstract In this paper we propose a conditional distribution of the waiting time given the queue length. We assume that the number of customers in a queue, that is the queue length, follows a geometric distribution and the waiting time of a newly arrived customer in a queue follows an exponential distribution. We model the conditional distribution of the waiting time given the queue length using Gumbel's bivariate exponential copula. Parameters are estimated using the likelihood approach with a two stage estimation procedure. A simulation study indicates the performance of the estimators. Asymptotic properties of the estimators of the parameters are studied. We apply the model to a real data set to illustrate the dependence between the waiting time and the queue length.
CD47 Expression Defines Efficacy of Rituximab with CHOP in Non–Germinal Center B-cell (Non-GCB) Diffuse Large B-cell Lymphoma Patients (DLBCL), but Not in GCB DLBCL

High CD47 expression impacts survival of patients with non-germinal center, but not germinal center, diffuse large B-cell lymphoma treated with rituximab plus standard chemotherapy. Blocking CD47 in vitro enhanced phagocytosis of rituximab-mediated phagocytosis in only non-GCB cell lines. Addition of rituximab (R) to “CHOP” (cyclophosphamide, doxorubicin, vincristine, and prednisone) chemotherapy improved outcome for diffuse large B-cell lymphoma (DLBCL) patients. Approximately 40% of patients who receive R-CHOP still succumb to disease due to intrinsic resistance or relapse. A potential negative regulator of DLBCL treatment outcome is the CD47 “don't eat me” immune checkpoint. To delineate the impact of CD47, we used a clinically and molecularly well-annotated cohort of 939 DLBCL patients, comprising both germinal center B-cell (GCB) and non-GCB DLBCL subtypes, treated with either CHOP or R-CHOP. High (above median) CD47 mRNA expression correlated with a detrimental effect on overall survival (OS) when DLBCL patients received R-CHOP therapy (P = 0.001), but not CHOP therapy (P = 0.645). Accordingly, patients with low CD47 expression benefited most from the addition of rituximab to CHOP [HR, 0.32; confidence interval (CI), 0.21–0.50; P < 0.001]. This negative impact of high CD47 expression on OS after R-CHOP treatment was only evident in cancers of non-GCB origin (HR, 2.09; CI, 1.26–3.47; P = 0.004) and not in the GCB subtype (HR, 1.16; CI, 0.68–1.99; P = 0.58). This differential impact of CD47 in non-GCB and GCB was confirmed in vitro, as macrophage-mediated phagocytosis stimulated by rituximab was augmented by CD47-blocking antibody only in non-GCB cell lines. Thus, high expression of CD47 mRNA limited the benefit of addition of rituximab to CHOP in non-GCB patients, and CD47-blockade only augmented rituximab-mediated phagocytosis in non-GCB cell lines. Patients with non-GCB DLBCL may benefit from CD47-targeted therapy in addition to rituximab.
UBC‐Nepal Expedition: Haemoconcentration underlies the reductions in cerebral blood flow observed during acclimatization to high altitude

What is the central question of this study? The aim was to evaluate the degree to which increases in haematocrit alter cerebral blood flow and cerebral oxygen delivery during acclimatization to high altitude. What is the main finding and its importance? Through haemodilution, we determined that, after 1 week of acclimatization, the primary mechanism contributing to the cerebral blood flow response during acclimatization is an increase in haemoglobin and haematocrit. The remaining contribution to the cerebral blood flow response during acclimatization is likely to be attributable to ventilatory acclimatization.
Herbal Medicine Containing Aristolochic Acid and the Risk of Primary Liver Cancer in Patients with Hepatitis C Virus Infection

Background: We investigated the association between taking herbal medicine (HM) containing aristolochic acid (AA) and the risk of primary liver cancer (PLC) among patients with hepatitis C virus (HCV) infection. Methods: This is a prospective study for the long-term follow-up of a nationwide population-based cohort of patients ages 18 years or older diagnosed with HCV infection during 1997 to 2010. A total of 223,467 HCV-infected patients were identified using the National Health Insurance Research Database in Taiwan. The use of HM containing AA was evaluated among patients who had visited traditional Chinese medicine clinics beginning from 1997 to 1 year prior to the diagnosis of PLC or dates censored (2003). We tracked each individual patient from 1997 to 2013 to identify incident cases of PLC since 1999. Results: During the follow-up period of 3,052,132 person-years, we identified 25,502 PLC cases; this corresponded to an overall incidence rate of 835.5 PLCs per 100,000 person-years. The adjusted HRs were 1.21 [95% confidence interval (CI), 1.18–1.24], 1.48 (95% CI, 1.37–1.59), 1.50 (95% CI, 1.34–1.68), and 1.88 (95% CI, 1.61–2.19) for estimated AA usage groups: 1 to 250, 251 to 500, 501 to 1,000, and more than 1,000 mg, respectively, relative to no AA exposure (reference group). Conclusions: The current findings suggest that among HCV-positive patients, increasing exposure to AA poses an increased risk of acquiring PLC. Impact: AA may increase the risk of PLC in HCV-positive populations.
Determination of Ochratoxin A (OTA), Ochratoxin B (OTB), T-2, and HT-2 Toxins in Wheat Grains, Wheat Flour, and Bread in Lebanon by LC-MS/MS

Cereals are prone to fungal infection during growth, harvesting, transportation, and/or storage. As a result, cereals such as wheat grains and wheat-derived products may be contaminated with mycotoxins leading to acute and chronic health exposure. The current study investigated the presence of the mycotoxins: ochratoxin A (OTA), ochratoxin B (OTB), T-2, and HT-2 toxins in samples of wheat grains (n = 50), wheat flour (n = 50), and bread (n = 37) from the main mills in Lebanon using LC-MS/MS. Accuracy ranged from 98–100%, recoveries from 93–105%, and intraday and interday precision were 5–7% and 9–12%, respectively. The tested wheat grains, wheat flour, and bread samples did not contain detectable levels of T-2 and HT-2 toxins and OTB. Four wheat flour samples (8% of flour samples) showed positive OTA levels ranging from 0.6–3.4 μg·kg−1 with an arithmetic mean of 1.9 ± 0.2 μg·kg−1. Only one sample contained an OTA concentration greater than the limit set by the European Union (3 μg·kg−1) for wheat-derived products. This study suggests that mycotoxin contamination of wheat grains, wheat flour, and bread in Lebanon is currently not a serious public health concern. However, surveillance strategies and monitoring programs must be routinely implemented to ensure minimal mycotoxin contamination of wheat-based products.
Clinical significance of serum MicroRNA-203 in patients with acute myeloid leukemia

Statement of Retraction We, the Editor, Publisher and author, have retracted the following article from Bioengineered: Yingmeng Guo, Clinical significance of serum MicroRNA-203 in patients with acute myeloid leukemia, Bioengineered, 2019;10(1): 345-352, DOI 10.1080/21655979.2019. 1652490 The above article has been retracted as, subsequent to publication, significant overlap in text, study and figures has been identified with the following earlier published article: Zhuanzhen Zheng, Gong Rong, Guoxia Li, Fanggang Ren, Yanping Ma, Diagnostic and prognostic significance of serum miR-203 in patients with acute myeloid leukemia, International Journal of Clinical and Experimental Pathology, 2019;12(5):1548-1556, DOI 1936-2625/IJCEP0092247 We have been informed in our decision-making by our policy on publishing ethics and integrity and the COPE guidelines on retractions. The retracted article will remain online to maintain the scholarly record, but it will be digitally watermarked on each page as ‘Retracted’.
Lipedema and Dercum's Disease: A New Application of Bioimpedance.

Background: Lipedema and Dercum's disease (DD) are incompletely characterized adipose tissue diseases, and objective measures of disease profiles are needed to aid in differential diagnosis. We hypothesized that fluid properties, quantified as tissue water bioimpedance in the upper and lower extremities, differ regionally between these conditions. Methods and Results: Women (cumulative n = 156) with lipedema (n = 110), DD (n = 25), or without an adipose disease matched for age and body mass index to early stage lipedema patients (i.e., controls n = 21) were enrolled. Bioimpedance spectroscopy (BIS) was applied to measure impedance values in the arms and legs, indicative of extracellular water levels. Impedance values were recorded for each limb, as well as the leg-to-arm impedance ratio. Regression models were applied to evaluate hypothesized relationships between impedance and clinical indicators of disease (significance criteria: two-sided p < 0.05). Higher extracellular water was indicated (i) in the legs of patients with higher compared with lower stages of lipedema (p = 0.03), (ii) in the leg-to-arm impedance ratio in patients with lipedema compared with patients with DD (p ≤ 0.001), and (iii) in the leg-to-arm impedance ratio in patients with stage 1 lipedema compared with controls (p ≤ 0.01). Conclusion: BIS is a noninvasive portable modality to assess tissue water, and this device is available in both specialized and nonspecialized centers. These findings support that regional bioimpedance measures may help to distinguish lipedema from DD, as well as to identify early stages of lipedema.
A review of the putative causal mechanisms associated with lower macular pigment in diabetes mellitus

Abstract Macular pigment (MP) confers potent antioxidant and anti-inflammatory effects at the macula, and may therefore protect retinal tissue from the oxidative stress and inflammation associated with ocular disease and ageing. There is a body of evidence implicating oxidative damage and inflammation as underlying pathological processes in diabetic retinopathy. MP has therefore become a focus of research in diabetes, with recent evidence suggesting that individuals with diabetes, particularly type 2 diabetes, have lower MP relative to healthy controls. The present review explores the currently available evidence to illuminate the metabolic perturbations that may possibly be involved in MP’s depletion. Metabolic co-morbidities commonly associated with type 2 diabetes, such as overweight/obesity, dyslipidaemia, hyperglycaemia and insulin resistance, may have related and independent relationships with MP. Increased adiposity and dyslipidaemia may adversely affect MP by compromising the availability, transport and assimilation of these dietary carotenoids in the retina. Furthermore, carotenoid intake may be compromised by the dietary deficiencies characteristic of type 2 diabetes, thereby further compromising redox homeostasis. Candidate causal mechanisms to explain the lower MP levels reported in diabetes include increased oxidative stress, inflammation, hyperglycaemia, insulin resistance, overweight/obesity and dyslipidaemia; factors that may negatively affect redox status, and the availability, transport and stabilisation of carotenoids in the retina. Further study in diabetic populations is warranted to fully elucidate these relationships.
Building complex life through self-organization.

Cells are inherently conferred with the ability to self-organize into the tissues and organs comprising the human body. Self-organization can be recapitulated in vitro and recent advances in the organoid field are just one example of how we can generate small functioning elements of organs. Tissue engineers can benefit from the power of self-organization and should consider how they can harness and enhance the process with their constructs. For example, aggregates of stem cells and tissue-specific cells benefit from the input of carefully selected biomolecules to guide their differentiation towards a mature phenotype. This can be further enhanced by the use of technologies to provide a physiological microenvironment for self-organization, enhance the size of the constructs, and enable the long-term culture of self-organized structures. Importantly, conducting self-organization should be limited to fine-tuning and should avoid over-engineering that could counteract the power of inherent cellular self-organization.
DESIGN AND IMPLEMENTATION OF RASP IN DATA COMMOTION IN BUILDING ARCANE AND CAPABILITY QUERY SERVICES

Because of distinctive advantages in scalability and price-saving, storing of understanding-intensive query services in cloud gets increasingly popular. We setup random space perturbation system to produce realistic range query and k nearest-neighbour services of query in cloud. The forecasted approach will undertake data confidentiality, privacy of query, efficient processing of query furthermore to lessen in-house price of processing, and obtain a great balance within it. Random space perturbation system is a kind of growing perturbation, by mixture of order preserving file encryption, random noise injection, and random project. Random space perturbation system encloses lots of significant features. The fundamental proposal should be to at random modify complex data sets by grouping of order preserving file encryption, random noise injection, random project and dimensionality expansion, to make sure that utility for handing range queries is preserved.
Optimization of Enniatin Production by Solid-Phase Fermentation of Fusarium tricinctum

Enniatins are cyclic depsipeptides produced by fungi of the genus Fusarium that are of interest due to their pronounced biological activities; especially enniatins A, A1, B, and B1 possess anticarcinogenic and anti-HIV properties. In the present study, F. tricinctum was grown on seven solid media and in one liquid growth medium with or without addition of peptone or of amino acid precursors in order to identify favourable media with simple cultivation conditions for maximum enniatin production. Additionally, the optimal duration of growth was investigated for the highest yields of enniatins. From the different media analysed, white beans (Phaseolus vulgaris, solid medium) induced the highest accumulation of enniatins A, A1, B, and B1, that reached a maximum of 1,365 mg total enniatins in 1 L growth medium after 18 days of fermentation. Fermentation of F. tricinctum on white beans gave the highest yield of enniatins compared to all other media analysed in this study.
Modeling and prediction of ice hockey match results

Abstract Modeling and prediction of ice hockey match results are not as widely examined areas as modeling and prediction of association football match results. It is assumed that match results in football and ice hockey can be modeled by the bivariate Poisson distribution or by some modification of this distribution. The aim of this paper is to explore the possibility of using models derived for football match results also for ice hockey match results and to propose some modifications of these models. A new model based on alternative definition of the bivariate Poisson distribution is presented. The models are tested on historical data from the highest-level ice hockey league in the Czech Republic between the years 1999 and 2012.
Resource Dependence and the Exits of Young Firms

Abstract Which entrepreneurial firms exit by merger or sale, and which exit by closing? We draw on resource dependence theory in order to explore how new venture dependencies on the founder and industry affect the type of firm exit. While previous researchers have concluded that early stage firms rely on the human capital of the entrepreneur to survive and thrive, we suggest that certain dependencies can act as barriers to exit through a merger or a sale. Likewise, we suggest that industries that are low tech and industries that experience high firm turnover create dependencies on the local market, and exit is less likely by a sale or a merger. We test our model using binary logistic regression on a 2012 sample from the Kauffman Firm Survey of 451 firms founded in 2004. We find that firms that are operated as sole proprietorships and firms that are operated out of the primary owner’s home are significantly, negatively related to exit by a merger or a sale. Firms operating in high-tech industries are significantly, positively related to exit by a merger or a sale. These findings hold even when controlling for the size, performance, and competitive advantage of the exiting firms. Our findings offer preliminary evidence that resource dependencies affect exit outcomes.
Exploring plasticity in the development path of the automotive industry in Baden-Württemberg: the role of combinatorial knowledge dynamics

Abstract Profound insights into why some regional paths remain dynamic over several decades while others follow a bumpy road and become stuck in the past are still scarce. This paper addresses this gap by contributing to a deeper understanding of dynamics within territorial paths. It focuses on organizational and institutional changes connected with so-called combinatorial knowledge dynamics. We claim that especially innovations based on the transversal combination of separated knowledge bases are connected to the gradual transformation, recombination or creation of institutions at the microlevel. This contribution explores the dynamics within the automotive industry of Baden-Württemberg by providing a meso-level overview of the trajectory of its technological and institutional development as well as an analysis of a case study that illustrates the gradual institutional change on the micro-level in the course of knowledge combination.
Trying to put a name tag on Subjective Wellbeing

Abstract Over the last three decades there has been a growing interest in the field of subjective wellbeing (SWB). With the emergence of happiness economics researchers have exploring the possibility of using subjective wellbeing indicators for potential policy implications. However, despite the expanding literature on the subject there is no clear definition of subjective wellbeing, or indicators such as life satisfaction or happiness.
The Business Community To Support The Training Of Prospective Students/Employees

Abstract In the past years, theoretical high-school education in Romania has gone through much public criticism regarding both the quality and the effectiveness of the instruction offered to students. An excessive focus on theory for most subjects and the neglect of the practical aspects/applications of the themes studied are known to have had negative effects on students’ motivation and their ability to choose a career and to adapt to the labour market requirements. The authors of this article intend primarily to briefly analyse some of the curricular aspects underlining this problem and to suggest some opportunities to offset this situation – opportunities derived from the business community and within the reach of the theoretical high-schools’ managers. In support of the proposed solutions, the authors are going to examine two types of initiatives implemented at the “Gheorghe Lazăr” National College from Sibiu: “training placement” in EU-funded Leonardo da Vinci projects and a “work-experience” type of initiative leading to a successful programme run every school year in cooperation with firms, institutions, and companies from Sibiu.
The private enforcement of the MiFID conduct of business rules. An overview of the Italian and Spanish experiences

The article analyses the impact of the MiFID conduct of business rules on national contract law. EU financial regulatory law is driven by a public-oriented approach and does not provide private law remedies for investors vis-à- vis the investment firms. At EU level, the breach of the conduct of business rules gives rise only to public-administrative sanctions. Whereas supervision and public enforcement are vertically-centralised, private enforcement is horizontally-decentralised. Against this backdrop, it is argued that European regulatory and national contract law do not represent two separated and isolated ‘entities’. Starting from the Italian and Spanish experiences, it is submitted that national courts and other private enforcement mechanisms (eg ADR, arbitration) interpret national contract law in light of the financial regulatory law providing effective remedies to the investors.