Miracle-dz/UniFAR-FTUs huggingface dataset:
Local rewiring algorithms to increase clustering and grow a small world

Many real-world networks have high clustering among vertices: vertices that share neighbours are often also directly connected to each other. A network’s clustering can be a useful indicator of its connectedness and community structure. Algorithms for generating networks with high clustering have been developed, but typically rely on adding or removing edges and nodes, sometimes from a completely empty network. Here, we introduce algorithms that create a highly clustered network by starting with an existing network and rearranging edges, without adding or removing them; these algorithms can preserve other network properties even as the clustering increases. They rely on local rewiring rules, in which a single edge changes one of its vertices in a way that is guaranteed to increase clustering. This greedy step can be applied iteratively to transform a random network into a form with much higher clustering. Additionally, the algorithms presented grow a network’s clustering faster than they increase its path length, meaning that network enters a regime of comparatively high clustering and low path length: a small world. These algorithms may be a basis for how real-world networks rearrange themselves organically to achieve or maintain high clustering and small-world structure.
Use of Attenuated but Metabolically Competent Salmonella as a Probiotic To Prevent or Treat Salmonella Infection

ABSTRACT Salmonella enterica is among the most burdensome of foodborne disease agents. There are over 2,600 serovars that cause a range of disease manifestations ranging from enterocolitis to typhoid fever. While there are two vaccines in use in humans to protect against typhoid fever, there are none that prevent enterocolitis. If vaccines preventing enterocolitis were to be developed, they would likely protect against only one or a few serovars. In this report, we tested the hypothesis that probiotic organisms could compete for the preferred nutrient sources of Salmonella and thus prevent or treat infection. To this end, we added the fra locus, which encodes a utilization pathway for the Salmonella-specific nutrient source fructose-asparagine (F-Asn), to the probiotic bacterium Escherichia coli Nissle 1917 (Nissle) to increase its ability to compete with Salmonella in mouse models. We also tested a metabolically competent, but avirulent, Salmonella enterica serovar Typhimurium mutant for its ability to compete with wild-type Salmonella. The modified Nissle strain became more virulent and less able to protect against Salmonella in some instances. On the other hand, the modified Salmonella strain was safe and effective in preventing infection with wild-type Salmonella. While we tested for efficacy only against Salmonella Typhimurium, the modified Salmonella strain may be able to compete metabolically with most, if not all, Salmonella serovars, representing a novel approach to control of this pathogen.
Associations between Race and Dementia Status and the Quality of End-of-Life Care.

BACKGROUND Non-Hispanic black and dementia patients receive more invasive and futile treatment at end of life (EOL) relative to others. Little is known about the relationship between race/ethnicity, dementia, and EOL care quality. OBJECTIVE Identify the relationship between race/ethnicity, dementia, and proxy reporters' evaluation of EOL care quality in older adults. DESIGN Latent class analysis (LCA) of national survey data. SETTING 1588 deceased Medicare beneficiaries age 65 and older from the National Health and Aging Trends Study (2011-2016). MEASUREMENTS LCA identified three types of quality EOL care using nine measures of symptom management, quality of healthcare encounters, and dignified treatment. Race and dementia were primary predictors of EOL care quality type. Adjusted models controlled for decedent education, sex, marital status, age, number of illnesses, number of hospitalizations, self-rated health, place of death, hospice involvement, and proxy relationship to decedent and familiarity with care. RESULTS Over 20% of proxies report that dying individuals experienced suboptimal EOL care quality, characterized by pain, sadness, poor communication, and inattention to personal care needs. In adjusted analyses, proxies for non-Hispanic black decedents were less likely to provide negative care assessments than proxies for non-Hispanic white decedents (adjusted odds ratio [AOR]: 0.58; 95% confidence interval [CI]: 0.40-0.86). Proxies for decedents with dementia were less likely to provide negative assessments than proxies for decedents without dementia (AOR: 0.70; 95% CI: 0.51-0.97). IMPLICATIONS Efforts to improve EOL care quality are needed. More positive EOL care quality assessments for non-Hispanic Black and dementia decedents appear counterintuitive given research demonstrating that these groups of individuals are likely to have received suboptimal EOL care. Because caregiver expectations for care may differ by decedent race and dementia status, research is needed to explore the role of caregiver expectations for EOL care to explain these paradoxical findings.
Persistent response of Fanconi anemia haematopoietic stem and progenitor cells to oxidative stress

ABSTRACT Oxidative stress is considered as an important pathogenic factor in many human diseases including Fanconi anemia (FA), an inherited bone marrow failure syndrome with extremely high risk of leukemic transformation. Members of the FA protein family are involved in DNA damage and other cellular stress responses. Loss of FA proteins renders cells hypersensitive to oxidative stress and cancer transformation. However, how FA cells respond to oxidative DNA damage remains unclear. By using an in vivo stress-response mouse strain expressing the Gadd45β-luciferase transgene, we show here that haematopoietic stem and progenitor cells (HSPCs) from mice deficient for the FA gene Fanca or Fancc persistently responded to oxidative stress. Mechanistically, we demonstrated that accumulation of unrepaired DNA damage, particularly in oxidative damage-sensitive genes, was responsible for the long-lasting response in FA HSPCs. Furthermore, genetic correction of Fanca deficiency almost completely abolished the persistent oxidative stress-induced G2/M arrest and DNA damage response in vivo. Our study suggests that FA pathway is an integral part of a versatile cellular mechanism by which HSPCs respond to oxidative stress.
Tackling HIV Persistence: Pharmacological versus CRISPR-Based Shock Strategies

Jan Svoboda studied aspects of viral latency, in particular with respect to disease induction by avian RNA tumor viruses, which were later renamed as part of the extended retrovirus family. The course of retroviral pathogenesis is intrinsically linked to their unique property of integrating the DNA copy of the retroviral genome into that of the host cell, thus forming the provirus. Retroviral latency has recently become of major clinical interest to allow a better understanding of why we can effectively block the human immunodeficiency virus type 1 (HIV-1) in infected individuals with antiviral drugs, yet never reach a cure. We will discuss HIV-1 latency and its direct consequence—the formation of long-lasting HIV-1 reservoirs. We next focus on one of the most explored strategies in tackling HIV-1 reservoirs—the “shock and kill” strategy—which describes the broadly explored pharmacological way of kicking the latent provirus, with subsequent killing of the virus-producing cell by the immune system. We furthermore present how the clustered regularly interspaced palindromic repeats (CRISPR) and associated protein (Cas) system can be harnessed to reach the same objective by reactivating HIV-1 gene expression from latency. We will review the benefits and drawbacks of these different cure strategies.
A “Common Factors” Approach to Developing Culturally Tailored HIV Prevention Interventions

The current dominant model of HIV prevention intervention dissemination involves packaging interventions developed in one context, training providers to implement that specific intervention, and evaluating the extent to which providers implement it with fidelity. Research shows that providers rarely implement these programs with fidelity due to perceived incompatibility, resource constraints, and preference for locally generated solutions. In this study, we used the concept of “common factors,” or broad constructs shared by most evidence-based HIV prevention interventions, to train service providers to develop their own programs. We recruited eight Ukrainian HIV prevention organizations from regions with HIV epidemics concentrated among people who inject drugs. We trained staff to identify HIV risk behaviors and determinants, construct behavior change logic models, and develop and manualize an intervention. We systematically reviewed each manual to assess intervention format and content and determine whether the program met intervention criteria as taught during training. All agencies developed programs that reflected common factors of effective behavior change HIV prevention interventions. Each agency’s program targeted a unique population that reflected local HIV epidemiology. All programs incorporated diverse pedagogical strategies that focused on skill-building, goal-setting, communication, and empowerment. Agencies struggled to limit information dissemination and the overall scope and length of their programs. We conclude that training service providers to develop their own programs based on common elements of effective behavior change interventions can potentially transform existing processes of program development, implementation, and capacity building. Expanding this model will require committed training and support resources.
A CAD Open Platform for High Performance Reconfigurable Systems in the EXTRA Project

As the power wall has become one of the main limiting factors for the performance of general purpose processors, the trend in High Performance Computing (HPC) is moving towards application-specific accelerators in order to meet the stringent performance requirements for exascale computing while still satisfying power budget constraints. Within this context, reconfigurable devices, and more specifically FPGA-based systems, represent a promising solution able to achieve highly energy efficient computations without jeopardizing performance. Nevertheless, the exploitation of reconfigurable hardware is still limited due to the hardware-software co-design challenges that it poses, the time consuming design space exploration process and the programming complexity. To overcome these challenges, the EXTRA European project addresses the reconfigurability of such devices as a first-class feature, covering the entire stack from the system architecture up to the application. Within this paper, we present the effort of the EXTRA project towards the definition of an adaptive open platform for the optimization and implementation of applications on high performance reconfigurable architectures. The underlying infrastructure of the platform is here presented, highlighting its capability to integrate modules from different developers in order to stimulate external contributions and open research.
Environmental Stigma

This article examined the extent to which residents living in the Midland–Saginaw–Bay City area in Eastern Michigan felt stigmatized due to industrial contamination. Seventy in-depth interviews were conducted with local residents, focusing on the extent to which they experienced three aspects of stigma—affective, cognitive, and behavioral. Results indicated that although some participants were not concerned with living in a contaminated community, local residents largely perceived dioxin as a risk to individual health and the local environment. Concern, shock, and irritation were typical affective responses at the time participants learned of the contamination. Several participants indicated a feeling of embarrassment and fear of being rejected by others because of the stigma associated with industrial contamination. Instead of actively seeking information about dioxin contamination and remediation, participants often relied on information provided to them by government officials. Behaviorally, participants avoided eating locally caught fish and prepared fish more carefully in order to avoid exposure to contaminants. As a whole, this study provided insight to understand affective, cognitive, and behavioral responses to environmental stigma.
Genome-wide determination of on-target and off-target characteristics for RNA-guided DNA methylation by dCas9 methyltransferases

Abstract Background Fusion of DNA methyltransferase domains to the nuclease-deficient clustered regularly interspaced short palindromic repeat (CRISPR) associated protein 9 (dCas9) has been used for epigenome editing, but the specificities of these dCas9 methyltransferases have not been fully investigated. Findings We generated CRISPR-guided DNA methyltransferases by fusing the catalytic domain of DNMT3A or DNMT3B to the C terminus of the dCas9 protein from Streptococcus pyogenes and validated its on-target and global off-target characteristics. Using targeted quantitative bisulfite pyrosequencing, we prove that dCas9-BFP-DNMT3A and dCas9-BFP-DNMT3B can efficiently methylate the CpG dinucleotides flanking its target sites at different genomic loci (uPA and TGFBR3) in human embryonic kidney cells (HEK293T). Furthermore, we conducted whole genome bisulfite sequencing (WGBS) to address the specificity of our dCas9 methyltransferases. WGBS revealed that although dCas9-BFP-DNMT3A and dCas9-BFP-DNMT3B did not cause global methylation changes, a substantial number (more than 1000) of the off-target differentially methylated regions (DMRs) were identified. The off-target DMRs, which were hypermethylated in cells expressing dCas9 methyltransferase and guide RNAs, were predominantly found in promoter regions, 5΄ untranslated regions, CpG islands, and DNase I hypersensitivity sites, whereas unexpected hypomethylated off-target DMRs were significantly enriched in repeated sequences. Through chromatin immunoprecipitation with massive parallel DNA sequencing analysis, we further revealed that these off-target DMRs were weakly correlated with dCas9 off-target binding sites. Using quantitative polymerase chain reaction, RNA sequencing, and fluorescence reporter cells, we also found that dCas9-BFP-DNMT3A and dCas9-BFP-DNMT3B can mediate transient inhibition of gene expression, which might be caused by dCas9-mediated de novo DNA methylation as well as interference with transcription. Conclusion Our results prove that dCas9 methyltransferases cause efficient RNA-guided methylation of specific endogenous CpGs. However, there is significant off-target methylation indicating that further improvements of the specificity of CRISPR-dCas9 based DNA methylation modifiers are required.
Modified maxillary reconstruction technique for Brown's class III defects by subdividing a rhomboid shaped iliac crest into 2 subunits

Men and women share a common maxillary morphology with heterogeneity in size. This indicated that our technique of reconstruction with a rhomboid‐shaped iliac crest bone flap incorporating a 30° vertical wedge osteotomy may be widely used for Brown's class III maxillectomy defect reconstruction among a population with class I skeletal profile. The reconstruction of Brown's class III maxillary defects is extremely challenging. The purpose of this study was to closely study the maxilla geometrically in order to establish a standardized maneuver, which facilitates conversion of the iliac bone flap into a natural maxilla's contours.
Randomized, controlled trial of resistance training in breast cancer patients receiving adjuvant radiotherapy: results on cancer-related fatigue and quality of life.

BACKGROUND Exercise has been reported to decrease cancer-related fatigue and to increase quality of life (QoL) in various breast cancer (BC) populations. However, studies investigating exercise during radiotherapy or resistance training are scarce. We conducted a randomized, controlled trial (BEST study) to assess the efficacy of 12-week resistance training on fatigue beyond possible psychosocial effects of a group-based intervention. PATIENTS AND METHODS One hundred sixty patients with BC stage 0-III were randomly assigned to a 12-week progressive resistance training (2 times/week) or a 12-week relaxation control (RC, 2 times/week). Both interventions were group-based. The primary end point fatigue was assessed with a 20-item multidimensional questionnaire, QoL with EORTC questionnaires. Statistical analyses were based on analysis of covariance models for the individual changes from baseline to week 13. RESULTS Adherence to the intervention program as well as the completion rate (97%) for the primary outcome variable fatigue was high. In intention-to-treat analyses for the N = 155 patients, significant between-group mean differences (MD) favoring the exercise group (EX) were observed for general fatigue (P = 0.044), especially for the subscale physical fatigue [MD = -0.8; 95% confidence interval -1.5 to -0.2, P = 0.013], but not for affective (P = 0.91) or cognitive fatigue (P = 0.65). For QoL, significantly larger improvements regarding the role function (P = 0.035) and pain (P = 0.040) were noted among exercisers compared with RCs. Future perspective improved significantly stronger in the RC group compared with the EX group (P = 0.047). CONCLUSIONS The 12-week resistance training program was a safe, feasible and efficacious strategy to improve cancer-related fatigue and components of QoL in BC patients during adjuvant radiotherapy. As exercise was compared with another group-based intervention, results indicate that resistance training effects on fatigue and QoL go beyond psychosocial benefits, and that the clinically relevant overall benefit of resistance exercise compared with usual care can be assumed to be higher. TRIAL REGISTRATION ClinicalTrials.gov NCT01468766.
Automatic Depth Extraction from 2D Images Using a Cluster-Based Learning Framework

There has been a significant increase in the availability of 3D players and displays in the last years. Nonetheless, the amount of 3D content has not experimented an increment of such magnitude. To alleviate this problem, many algorithms for converting images and videos from 2D to 3D have been proposed. Here, we present an automatic learning-based 2D-3D image conversion approach, based on the key hypothesis that color images with similar structure likely present a similar depth structure. The presented algorithm estimates the depth of a color query image using the prior knowledge provided by a repository of color + depth images. The algorithm clusters this database attending to their structural similarity, and then creates a representative of each color-depth image cluster that will be used as prior depth map. The selection of the appropriate prior depth map corresponding to one given color query image is accomplished by comparing the structural similarity in the color domain between the query image and the database. The comparison is based on a K-Nearest Neighbor framework that uses a learning procedure to build an adaptive combination of image feature descriptors. The best correspondences determine the cluster, and in turn the associated prior depth map. Finally, this prior estimation is enhanced through a segmentation-guided filtering that obtains the final depth map estimation. This approach has been tested using two publicly available databases, and compared with several state-of-the-art algorithms in order to prove its efficiency.
Viewing pre-60S maturation at a minute’s timescale

Abstract The formation of ribosomal subunits is a highly dynamic process that is initiated in the nucleus and involves more than 200 trans-acting factors, some of which accompany the pre-ribosomes into the cytoplasm and have to be recycled into the nucleus. The inhibitor diazaborine prevents cytoplasmic release and recycling of shuttling pre-60S maturation factors by inhibiting the AAA-ATPase Drg1. The failure to recycle these proteins results in their depletion in the nucleolus and halts the pathway at an early maturation step. Here, we made use of the fast onset of inhibition by diazaborine to chase the maturation path in real-time from 27SA2 pre-rRNA containing pre-ribosomes localized in the nucleolus up to nearly mature 60S subunits shortly after their export into the cytoplasm. This allows for the first time to put protein assembly and disassembly reactions as well as pre-rRNA processing into a chronological context unraveling temporal and functional linkages during ribosome maturation.
Feature Engineering for Depression Detection in Social Media

This research is based on the CLEF/eRisk 2017 pilot task which is focused on early risk detection of depression. The CLEF/eRsik 2017 dataset consists of text examples collected from messages of 887 Reddit users. The main idea of the task is to classify users into two groups: risk case of depression and non-risk case. This paper considers different feature sets for depression detection task among Reddit users by text messages processing. We examine our bag-of-words, embedding and bigram models using the CLEF/eRisk 2017 dataset and evaluate the applicability of stylometric and morphological features. We also perform a comparison of our results with the CLEF/eRisk 2017 task report.
Influence of low spatial resolution a priori data on tropospheric NO 2 satellite retrievals

Abstract. The retrieval of tropospheric columns of NO2 and other trace gases from satellite observations of backscattered solar radiation relies on the use of accurate a priori information. The spatial resolution of current space sensors is often significantly higher than that of the a priori datasets used, introducing uncertainties from spatial misrepresentation. In this study, the effect of spatial under-sampling of a priori data on the retrieval of NO2 columns was studied for a typical coastal area (around San Francisco). High-resolution (15 × 15 km2) NO2 a priori data from the WRF-Chem model in combination with high-resolution MODIS surface reflectance and aerosol data were used to investigate the uncertainty introduced by applying a priori data at typical global chemical transport model resolution. The results show that the relative uncertainties can be large (more than a factor of 2 if all a priori data used is at the coarsest resolution) for individual measurements, mainly due to spatial variations in NO2 profile and surface albedo, with smaller contributions from aerosols and surface height changes. Similar sensitivities are expected for other coastal regions and localised sources such as power plants, highlighting the need for high-resolution a priori data in quantitative analysis of the spatial patterns retrieved from satellite observations of tropospheric pollution.