Miracle-dz/UniFAR-FTUs huggingface dataset:
KDM2A-dependent reduction of rRNA transcription on glucose starvation requires HP1 in cells, including triple-negative breast cancer cells

Triple-negative breast cancer (TNBC) is very aggressive and lacks specific therapeutic targets. Ribosome RNAs (rRNAs) are central components of ribosomes and transcribed in nucleoli, and the level of rRNA transcription greatly affects ribosome production and cell proliferation. We have reported that an epigenetic protein, KDM2A, exists in nucleoli and reduces rRNA transcription on glucose starvation. However, the molecular mechanism is still unclear. The purpose of this study is to examine the KDM2A-dependent regulation mechanism of rRNA transcription. In this study, we turned our attention to the nucleolar accumulation of KDM2A. We found that KDM2A had multiple regions for its nucleolar localization, and one of the regions was directly bound by heterochromatin protein 1γ (HP1γ) using valine 801 in the LxVxL motif of KDM2A. A knockdown of HP1γ or a point mutation of valine 801 in KDM2A decreased the nucleolar accumulation of KDM2A, and suppressed the reduction of rRNA transcription on glucose starvation. These results uncovered a novel function of HP1γ: the regulation of rRNA transcription, and suggested that HP1γ stimulates the nucleolar accumulation of KDM2A to support the KDM2A-dependent regulation of rRNA transcription. HP1γ was expressed in cancer cells in all breast carcinoma tissues examined, including TNBC tissues. A knockdown of HP1γ in a TNBC cell line, MDA-MB-231 cells, reduced the nucleolar accumulation of KDM2A, and suppressed the reductions of rRNA transcription and cell proliferation on glucose starvation. These results suggest that the KDM2A-dependent regulation of rRNA transcription requires HP1γ, and thus may be applicable to the treatment of TNBC.
Investigation of MiR-92a as a Prognostic Indicator in Cancer Patients: a Meta-Analysis

Background: MiR-92a has been discovered to be involved in the malignant behavior of various types of cancers. However, the particular clinical and prognostic roles of miR-92a in tumors still need to be identified more precisely. The current meta-analysis assessed the prognostic value of miR-92a in various carcinomas. Methods: Systematic literature searches of PubMed, PMC, Web of Science (WOS), Embase in English and Wanfang, SinoMed and the China National Knowledge Infrastructure (CNKI) in Chinese up to Jan 15th 2019 were conducted for eligible studies. Twenty studies involving a total of 2573 patients were included in the analysis. Pooled hazard ratios (HR) for overall survival (OS) and disease-free survival (DFS), progression-free survival (PFS) and recurrence-free survival (RFS) were assessed using fixed-effects and random-effects models. Meta-regression and subgroup analyses were carried out to explore the source of heterogeneity. Odds ratio (OR) and 95%CIs were applied to evaluate the relationship between miR-92a expression levels and clinicopathological characteristics. Results: A significant association between miR-92a levels and OS (HR=2.18) was identified. The random pooling model also revealed significance of consistency (HR=2.14), indicating that the stability of the results. Subgroup analyses were performed and the corresponding significance was recognized in Chinese cancer patients (HR=2.35), studies of specimen derived from tissues (HR=2.43), non-hematological cancer (HR=2.35), osteosarcoma (HR=2.54), non-small cell lung cancer (HR=2.33), hepatocellular carcinoma (HR=2.40) and so on. There were significant relations observed of the expression level of miR-92a to tumor size (≥5 vs <5 cm) (OR=2.13), lymph node metastasis (present vs. absent) (OR=1.87), distant metastasis (present vs. absent) (OR=2.99) and so on. Conclusions: the over expression of miR-92a is associated with unfavorable prognosis of Chinese cancer patients. In addition, patients of elevated miR-92a expression level are likely to develop the cancers of more malignant behaviors.
Record Purcell factors in ultracompact hybrid plasmonic ring resonators

The experimental realization of micrometer-scale, long-range plasmonic ring resonators with ultrahigh Purcell factor is reported. For integrated optical devices and traveling-wave resonators, realistic use of the superior wave-matter interaction offered by plasmonics is impeded by ohmic loss, which increases rapidly with mode volume reduction. In this work, we report composite hybrid plasmonic waveguides (CHPWs) that are not only capable of guiding subwavelength optical mode with long-range propagation but also unrestricted by stringent requirements in structural, material, or modal symmetry. In these asymmetric CHPWs, the versatility afforded by coupling dissimilar plasmonic modes provides improved fabrication tolerance and more degrees of device design optimization. Experimental realization of CHPWs demonstrates propagation loss and mode area of 0.03 dB/μm and 0.002 μm2, corresponding to the smallest combination among long-range plasmonic structures reported to date. CHPW ring resonators with 2.5-μm radius were realized with record Purcell factor compared with existing plasmonic and dielectric resonators of similar radii.
Identifying and resolving the frustrations of reviewing the improvement literature: The experiences of two improvement researchers

Background and aims Summarising quality improvement (QI) research through systematic literature review has great potential to improve patient care. However, heterogeneous terminology, poor definition of QI concepts and overlap with other scientific fields can make it hard to identify and extract data from relevant literature. This report examines the compromises and pragmatic decisions that undertaking literature review in the field of QI requires and the authors propose recommendations for literature review authors in similar fields. Methods Two authors (EJ and JF) provide a reflective account of their experiences of conducting a systematic literature review in the field of QI. They draw on wider literature to justify the decisions they made and propose recommendations to improve the literature review process. A third collaborator, (WC) co-created the paper challenging author’s EJ and JF views and perceptions of the problems and solutions of conducting a review of literature in QI. Results Two main challenges were identified when conducting a review in QI. These were defining QI and selecting QI studies. Strategies to overcome these problems include: select a multi-disciplinary authorship team; review the literature to identify published QI search strategies, QI definitions and QI taxonomies; Contact experts in related fields to clarify whether a paper meets inclusion criteria; keep a reflective account of decision making; submit the protocol to a peer reviewed journal for publication. Conclusions The QI community should work together as a whole to create a scientific field with a shared vision of QI to enable accurate identification of QI literature. Our recommendations could be helpful for systematic reviewers wishing to evaluate complex interventions in both QI and related fields.
Finding Erroneous Components from Change Coupled Relations at Fix-inducing Changes

—During the gradual process of software evolution, errors appear in different components of a software system. These errors are later on ﬁxed by developers as part of corrective maintenance activities. However, if errors appear continuously from a particular component, that may indicate design ﬂaws or code smells. Maintenance cost will greatly reduce if design ﬂaws are treated as early as possible. To ﬁnd out such ﬂaws it may require time-consuming manual inspections. This paper tries to ﬁnd out such components using the information of change coupled cluster of ﬁles or Java classes at ﬁx-inducing changes. In this proposed approach, information (like class, method, parameter of method and variable names) from change coupled relation of a class at Fix-Inducing Changes (FICs) are used to provide information about erroneous components. Then the error history, of software components, is found by using cosine similarity of information from change coupled cluster of classes found in FICs to see with the architectural information found from authenticated sources. Finally, the error history of components is shown as the percentage of change coupled cluster of a class found in FICs of each 100 commits in the version control system
The method ADAMONT v1.0 for statistical adjustment of climate projections applicable to energy balance land surface models

We introduce the method ADAMONT v1.0 to adjust and disaggregate daily climate projections from a regional climate model against an observational dataset at hourly time resolution. The method uses a refined quantile mapping approach for statistical adjustment and an analogous method for sub-daily disaggregation. The method produces ultimately adjusted hourly time series of temperature, precipitation, wind speed, humidity, and short- and longwave radiation, which can in turn be used to force any energy balance land surface model. While the method is generic and can be employed on any appropriate observation time series, here we focus on the description and evaluation of the method in the French mountainous regions. The observational dataset used here is the SAFRAN meteorological reanalysis, which covers the entire French Alps split into 23 massifs, within which meteorological conditions are provided for several 300 m elevation bands. In order to evaluate the skills of the method itself, it is applied to the ALADIN-Climate v5 RCM using the ERA-Interim reanalysis as boundary conditions, for the time period from 1980 to 2010. Results of the ADAMONT method are compared to the SAFRAN reanalysis itself. Various evaluation criteria are used for temperature, precipitation, but also snow depth, which is computed by the SURFEX/ISBA-Crocus model using the meteorological driving data from either the adjusted RCM data, or the SAFRAN reanalysis itself. The evaluation addresses in particular the time transferability of the method (using various learning/application time periods), the impact of the RCM grid point selection procedure for each massif/altitude band configuration, and the inter-variable consistency of the adjusted meteorological data generated by the method. Results show that the performance of the method is satisfactory, with similar or even better evaluation metrics than alternative methods. However, results for air temperature are generally better than for precipitation. Results in terms of snow depth are satisfactory, which can be viewed as indicating a reasonably good inter-variable consistency of the meteorological data produced by the method. In terms of temporal transferability (evaluated over time periods of 15 years only), results depend on the learning period. In terms of RCM grid point selection technique, the use of a complex RCM grid points selection technique, taking into account horizontal but also altitudinal proximity to SAFRAN massif centre points/altitude couples, generally degrades evaluation metrics for high altitudes, compared to a simpler grid point selection method based on horizontal distance.
Combining VSM and BTM to Improve Requirements Trace Links Generation

Trace links between software artifacts provide available traceability information and in-depth insights for different stakeholders. Unfortunately, establishing trace links is a fallible, tedious, and labor-intensive task. To alleviate these problems, many Information Retrieval (IR) methods, such as Vector Space Model (VSM), Latent Semantic Indexing (LSI) and their variants, have been proposed to establish trace links automatically. In recent years, short-text artifacts (or even lack of documentation) become a new trend as more and more software systems are developed abiding by agile methodologies. It makes the effects of traditional IR-based trace links generation methods even worse. In this paper, Biterm Topic Model (BTM), which is good at dealing with short text, is introduced to solve the problem. A hybrid method combining VSM and BTM is proposed to generate requirements trace links. The empirical experiments conducted on three real and frequently-used datasets indicate that the hybrid method can achieve better performance, and the results can reach the “acceptable level” directly. Keywords—requirements traceability, information retrieval, vector space model, biterm topic model, short-text artifacts
Software Engineering Risks from Technical Debt in the Representation of Product/ion Knowledge

— In the multi-disciplinary production systems engineering (PSE) process, software engineers depend on requirements and de-sign rationales coming from product and production process planning, summarized as product/ion knowledge. Unfortunately, the engineering artifacts coming from product/ion planning often represent important product/ion knowledge incompletely and not well integrated, leading to risks regarding software engineering quality. In this paper, we report on a case study at a large industrial PSE organization, investigating Technical Debt (TD) effects, items, and causes in PSE process documentation and configuration management according to the VDI guideline 3695 Part 2. We focus on requirements for and issues in the representation of product/ion knowledge in the engineering data provided to software engineers. Based on data elicited from PSE domain experts, we model TD concepts based on the Quality Function Deployment method as foundation for TD analysis and risk management. The initial validation with domain experts revealed how software engineers could benefit from improved product/ion knowledge modeling as foundation for better understanding the rationale of engineering design decisions.
Improving the evidence for indicator condition guided HIV testing in Europe: Results from the HIDES II Study – 2012 – 2015

Background It is cost-effective to perform an HIV test in people with specific indicator conditions (IC) with an undiagnosed HIV prevalence of at least 0.1%. Our aim was to determine the HIV prevalence for 14 different conditions across 20 European countries. Methods Individuals aged 18–65 years presenting for care with one of 14 ICs between January 2012 and June 2014 were included and routinely offered an HIV test. Logistic regression assessed factors associated with testing HIV positive. Patients presenting with infectious mononucleosis-like syndrome (IMS) were recruited up until September 2015. Results Of 10,877 patients presenting with an IC and included in the analysis, 303 tested positive (2.8%; 95% CI 2.5–3.1%). People presenting with an IC in Southern and Eastern Europe were more likely to test HIV positive as were people presenting with IMS, lymphadenopathy and leukocytopenia/ thrombocytopenia. One third of people diagnosed with HIV after presenting with IMS reported a negative HIV test in the preceding 12 months. Of patients newly diagnosed with HIV where data was available, 92.6% were promptly linked to care; of these 10.4% were reported lost to follow up or dead 12 months after diagnosis. Conclusion The study showed that 10 conditions had HIV prevalences > 0.1%. These 10 ICs should be adopted into HIV testing and IC specialty guidelines. As IMS presentation can mimic acute HIV sero-conversion and has the highest positivity rate, this IC in particular affords opportunities for earlier diagnosis and public health benefit.
TMA but not TMAO increases with age in rat plasma and affects smooth muscle cells viability.

It has been suggested that trimethylamine oxide (TMAO), a liver oxygenation product of gut bacteria-produced trimethylamine (TMA), is a marker of cardiovascular risk. However, mechanisms of the increase and biological effects of TMAO are obscure. Furthermore, the potential role of TMAO precursor, i.e. TMA has not been investigated. We evaluated the effect of age, a cardiovascular risk factor, on plasma levels of TMA and TMAO, gut bacteria composition, gut-to-blood penetration of TMA, histological and hemodynamic parameters in 3-month-old and 18-month-old, male, Sprague-Dawley and Wistar-Kyoto rats. Cytotoxicity of TMA and TMAO was studied in human vascular smooth muscle cells (hVSMCs). Older rats showed significantly different gut bacteria composition, a significantly higher guttoblood TMA penetration, and morphological and hemodynamic alterations in intestines. In vitro, TMA at concentration of 500 µmol/L (2-fold higher than in portal blood) decreased hVSMCs viability. In contrast, TMAO at 1000-fold higher concentration than physiological one, had no effect on hVSMCs viability. In conclusion, older rats show higher plasma level of TMA due to a "leaky gut". TMA but not TMAO affects hVSMCs viability. We propose that TMA but not TMAO may be a marker and mediator of cardiovascular risk.
Emergence and adaptive evolution of Nipah virus

Abstract Since its first emergence in 1998 in Malaysia, Nipah virus (NiV) has become a great threat to domestic animals and humans. Sporadic outbreaks associated with human‐to‐human transmission caused hundreds of human fatalities. Here, we collected all available NiV sequences and combined phylogenetics, molecular selection, structural biology and receptor analysis to study the emergence and adaptive evolution of NiV. NiV can be divided into two main lineages including the Bangladesh and Malaysia lineages. We formly confirmed a significant association with geography which is probably the result of long‐term evolution of NiV in local bat population. The two NiV lineages differ in many amino acids; one change in the fusion protein might be involved in its activation via binding to the G protein. We also identified adaptive and positively selected sites in many viral proteins. In the receptor‐binding G protein, we found that sites 384, 386 and especially 498 of G protein might modulate receptor‐binding affinity and thus contribute to the host jump from bats to humans via the adaption to bind the human ephrin‐B2 receptor. We also found that site 1645 in the connector domain of L was positive selected and involved in adaptive evolution; this site might add methyl groups to the cap structure present at the 5′‐end of the RNA and thus modulate its activity. This study provides insight to assist the design of early detection methods for NiV to assess its epidemic potential in humans.
Predictors of the Clinical Course of Tourette Syndrome: A Longitudinal Study

Objective: Tourette syndrome (TS) is a chronic childhood neurodevelopmental disorder characterized by motor and vocal tics and frequent comorbidities. The clinical presentation of Tourette syndrome is heterogeneous and the prognosis for each individual child is difficult to define. This large prospective longitudinal study explores predictors in childhood of the clinical course of tics and comorbidities in early adulthood. Methods: The cohort was recruited at the Danish National Tourette Clinic. Data were collected at baseline (N = 314; ages, 5-19 years) and follow-up 6 years later (n = 227; ages, 11-26 years) to examine changes in the expression of tics and comorbidities. Childhood clinical factors, represented by 4 binary clinical outcomes, were selected as possible predictors of the clinical course of tics and comorbidities in early adulthood; these were tic severity and diagnoses of obsessive compulsive disorder (OCD), attention-deficit hyperactivity disorder (ADHD), and emotional disorders. Results: The strongest predictors of high tic scores, OCD, or ADHD diagnoses in early adulthood were the corresponding tic (odds ratio [OR]: 1.09), OCD (OR: 1.08), and ADHD (OR: 1.13) severity scores (per scale point) in childhood. Being female (OR: 3.94) and childhood ADHD severity (OR: 1.11) predicted future emotional disorders. Special education, genetic factors, and psychosocial factors were also predictive for the clinical course of Tourette syndrome. Conclusion: We identified strong clinical predictors of Tourette syndrome–associated outcomes in early adulthood that are directly applicable to clinical Tourette syndrome populations and may help to guide new patients, plan early interventions, and implement preventive measures.
Comparative Immunogenicity of the 2014–2015 Northern Hemisphere Trivalent IIV and LAIV against Influenza A Viruses in Children

Both inactivated influenza vaccines (IIV) and live-attenuated influenza vaccines (LAIV) have been recommended for administration to children. Children are a high-risk group for severe influenza, and a major source of transmission. Therefore, prevention of infection by vaccination is particularly important. However, efficacy and immunogenicity of these vaccines are known to vary by season and geographic location. We compared the immunogenicity of the 2014–2015 Northern Hemisphere trivalent IIV and LAIV against influenza A virus in Canadian Hutterite children aged 2 to 17 using hemagglutination inhibition (HAI) assays, and enzyme-linked immunosorbent assays to measure hemagglutinin-specific serum IgA and mucosal IgA. Both vaccine formulations induced significant increases in HAI titers against H1N1 and H3N2 vaccine strains. Serum IgA titers against H3N2 were significantly boosted by both IIV and LAIV, while only IIV induced a significant increase in serum IgA specific to the H1N1 vaccine strain. While HAI titers correlated with protection conferred by IIV, mucosal IgA titers correlated with protection conferred by LAIV (mucosal IgA titers could not be established as a correlate for IIV due to sample size limitations). IIV and LAIV were previously reported to be equally efficacious in this cohort, although the immunogenicity of IIV was generally superior.
Prevalence of functional somatic syndromes and bodily distress syndrome in the Danish population: the DanFunD study

Aims: Little is known about the prevalence and characteristics of functional somatic syndromes (FSS) such as irritable bowel syndrome (IBS), fibromyalgia (FM), chronic fatigue syndrome (CFS), whiplash associated disorders (WAD), multiple chemical sensitivity (MCS), and bodily distress syndrome (BDS) in the general population when they are investigated simultaneously. Method: This cross-sectional study is based on the Danish Study of Functional Disorders (DanFunD) cohort consisting of 9656 adults from the general population. FSS and BDS were identified by questionnaires and characterized by age, sex, vocational training, physical health and comorbidity with physical and psychiatric disease. Results: In total, 16.3% (95% CI: 15.6–17.1) of the participants fulfilled the criteria for at least one FSS, ranging from 1.7% for WAD to 8.6% for CFS, and 16.1% (95% CI: 15.4–16.9) fulfilled the criteria for BDS. Cases had a high risk of poor self-perceived health, limitations in daily activities, and a high psychiatric comorbidity, all increasing with the number of syndromes in each individual. However, the associations differed across the various FSS. Mutual overlaps of IBS, FM and CFS were greater than could be expected by chance. Conclusions: FSS and BDS are prevalent in the adult Danish population, and cases have high risk of poor self-perceived health, limitation in daily activities, and psychiatric comorbidity. These associations were particularly strong for cases with multiple FSS and multi-organ BDS.