Miracle-dz/UniFAR-FTUs huggingface dataset:
Patient value: its nature, measurement, and role in real world evidence studies and outcomes-based reimbursement

Abstract The assessment of “patient value” is fundamental to clinical trials, real world evidence studies, and outcomes-based reimbursement schemes. Measures of health-related quality-of-life (HRQoL) are widely used in health research. Such measures are effective in determining the presence or absence of symptoms and functional ability. However, HRQoL measures were not intended, nor designed, to determine the value to patients of alternative health states. Functions have no intrinsic value—they are a means to fulfil human needs. However, needs can be met in a variety of ways, for example by adopting different functions or by the provision of social services. It is possible to analyze all functions in terms of the needs they satisfy. A needs model has been applied in health research since the 1990s. It is concerned with the extent to which human needs are fulfilled in the presence of disease and its treatment. It is argued that this is the major concern of the patient. Needs-based measures are patient-centric and produce a valid unidimensional index of outcome. Consequently, they provide a direct means of measuring patient value. This approach provides the possibility of evaluating health services in terms of the value they provide to consumers and payers. It also has a role to play in real-world evidence studies and outcomes-based reimbursement. It is recommended that greater attention is given in future to the development of patient-reported outcome measures that provide direct assessments of patient value.
A Scoring Tool to Identify East African HIV-1 Serodiscordant Partnerships with a High Likelihood of Pregnancy

Introduction HIV-1 prevention programs targeting HIV-1 serodiscordant couples need to identify couples that are likely to become pregnant to facilitate discussions about methods to minimize HIV-1 risk during pregnancy attempts (i.e. safer conception) or effective contraception when pregnancy is unintended. A clinical prediction tool could be used to identify HIV-1 serodiscordant couples with a high likelihood of pregnancy within one year. Methods Using standardized clinical prediction methods, we developed and validated a tool to identify heterosexual East African HIV-1 serodiscordant couples with an increased likelihood of becoming pregnant in the next year. Datasets were from three prospectively followed cohorts, including nearly 7,000 couples from Kenya and Uganda participating in HIV-1 prevention trials and delivery projects. Results The final score encompassed the age of the woman, woman’s number of children living, partnership duration, having had condomless sex in the past month, and non-use of an effective contraceptive. The area under the curve (AUC) for the probability of the score to correctly predict pregnancy was 0.74 (95% CI 0.72–0.76). Scores ≥7 predicted a pregnancy incidence of >17% per year and captured 78% of the pregnancies. Internal and external validation confirmed the predictive ability of the score. Discussion A pregnancy likelihood score encompassing basic demographic, clinical and behavioral factors defined African HIV-1 serodiscordant couples with high one-year pregnancy incidence rates. This tool could be used to engage African HIV-1 serodiscordant couples in counseling discussions about fertility intentions in order to offer services for safer conception or contraception that align with their reproductive goals.
Development and validation of a risk stratification score for new‐onset atrial fibrillation in STEMI patients undergoing primary percutaneous coronary intervention

New‐onset atrial fibrillation (NOAF) is a complication not infrequent in patients with acute ST‐segment elevation myocardial infarction (STEMI) undergoing primary percutaneous coronary intervention (pPCI) and has been associated with worse in‐hospital and long‐term prognosis. We aimed to develop and validate a risk score based on common clinical risk factors and routine blood biomarkers to assess the early incidence of NOAF post‐pPCI, before discharge.
Plant pathogens structure arthropod communities across multiple spatial and temporal scales

Plant pathogens and herbivores frequently co-occur on the same host plants. Despite this, little is known about the impact of their interactions on the structure of plant-based ecological communities. Here, we synthesize evidence that indicates that plant pathogens may profoundly impact arthropod performance, preference, population dynamics and community structure across multiple spatial and temporal scales. Intriguingly, the effects of plantpathogenherbivore interactions frequently cascade up and down multiple trophic levels and explain variation in the arthropod community at spatial scales ranging from patterns within single host plants to entire landscapes. This review indicates that knowledge on pathogenherbivore interactions may be crucial for understanding the dynamics of terrestrial communities.
Spatial eye–hand coordination during bimanual reaching is not systematically coded in either LIP or PRR

Significance When we reach for something, we also look at it. If we reach for two objects at once, one with each hand, we look first at one and then the other. It is not known which brain areas underlie this coordination. We studied two parietal areas known to be involved in eye and arm movements. Neither area was sensitive to the order in which the targets were looked at. This implies that coordinated saccades are driven by downstream areas and not by the parietal cortex as is commonly assumed. We often orient to where we are about to reach. Spatial and temporal correlations in eye and arm movements may depend on the posterior parietal cortex (PPC). Spatial representations of saccade and reach goals preferentially activate cells in the lateral intraparietal area (LIP) and the parietal reach region (PRR), respectively. With unimanual reaches, eye and arm movement patterns are highly stereotyped. This makes it difficult to study the neural circuits involved in coordination. Here, we employ bimanual reaching to two different targets. Animals naturally make a saccade first to one target and then the other, resulting in different patterns of limb–gaze coordination on different trials. Remarkably, neither LIP nor PRR cells code which target the eyes will move to first. These results suggest that the parietal cortex plays at best only a permissive role in some aspects of eye–hand coordination and makes the role of LIP in saccade generation unclear.
Transcriptional mutagenesis mediated by 8-oxoG induces translational errors in mammalian cells

Significance We had previously shown that 8-oxoG:A mismatch pairing can occur at both the DNA and RNA levels, thus causing base substitutions in DNA and translation errors, respectively. However, little attention has been paid to the biological significance of oxidized mRNA or to the clearance mechanism for such RNA lesions in mammalian cells. Here, we developed a sensitive reporter system to capture sequence-altered proteins that are translated from 8-oxoG–containing mRNAs. Also, we applied a deep-sequencing method to measure the content of these sequence-changed mRNAs to correlate the relationship between 8-oxoG–containing mRNAs and sequence-altered proteins. Additionally, we found that the accumulation of 8-oxoG in RNA can accelerate the production of pathogenic amyloid β peptides in mammalian cells. Reactive oxygen species formed within the mammalian cell can produce 8-oxo-7,8-dihydroguanine (8-oxoG) in mRNA, which can cause base mispairing during gene expression. Here we found that administration of 8-oxoGTP in MTH1-knockdown cells results in increased 8-oxoG content in mRNA. Under this condition, an amber mutation of the reporter luciferase is suppressed. Using second-generation sequencing techniques, we found that U-to-G changes at preassigned sites of the luciferase transcript increased when 8-oxoGTP was supplied. In addition, an increased level of 8-oxoG content in RNA induced the accumulation of aggregable amyloid β peptides in cells expressing amyloid precursor protein. Our findings indicate that 8-oxoG accumulation in mRNA can alter protein synthesis in mammalian cells. Further work is required to assess the significance of these findings under normal physiological conditions.
Molecular basis of hemoglobin adaptation in the high-flying bar-headed goose

During adaptive phenotypic evolution, some selectively fixed mutations may be directly causative and others may be purely compensatory. The relative contribution of these two classes of mutation depends on the form and prevalence of mutational pleiotropy. To investigate the nature of adaptive substitutions and their pleiotropic effects, we used a protein engineering approach to characterize the molecular basis of hemoglobin (Hb) adaptation in the bar-headed goose (Anser indicus), a hypoxia-tolerant species renowned for its trans-Himalayan migratory flights. We synthesized and tested all possible mutational intermediates in the line of descent connecting the wildtype bar-headed goose genotype with the most recent common ancestor of bar-headed goose and its lowland relatives. Site-directed mutagenesis experiments revealed effect-size distributions of causative mutations and biophysical mechanisms underlying changes in function. Trade-offs between alternative functional properties revealed the importance of compensating deleterious pleiotropic effects in the adaptive evolution of protein function.
Transient fibrosis resolves via fibroblast inactivation in the regenerating zebrafish heart

Significance After myocardial infarction in the mammalian heart, millions of cardiomyocytes are lost and replaced by fibrotic scar tissue. While fibrosis is persistent in adult mammals, there are some vertebrates, including zebrafish, with the capacity for regeneration. This process does not occur in the absence of fibrosis. Here we studied subpopulations of collagen-producing cells and analyzed their fate after complete regeneration of the zebrafish myocardium. Our data show that fibroblasts persisted in the regenerated heart but shut down the profibrotic program. While fibrosis could be considered as detrimental to the regeneration process, our study reveals a positive effect on cardiomyocyte proliferation. Accordingly, a fibrotic response can be beneficial for heart regeneration. In the zebrafish (Danio rerio), regeneration and fibrosis after cardiac injury are not mutually exclusive responses. Upon cardiac cryoinjury, collagen and other extracellular matrix (ECM) proteins accumulate at the injury site. However, in contrast to the situation in mammals, fibrosis is transient in zebrafish and its regression is concomitant with regrowth of the myocardial wall. Little is known about the cells producing this fibrotic tissue or how it resolves. Using novel genetic tools to mark periostin b- and collagen 1alpha2 (col1a2)-expressing cells in combination with transcriptome analysis, we explored the sources of activated fibroblasts and traced their fate. We describe that during fibrosis regression, fibroblasts are not fully eliminated but become inactivated. Unexpectedly, limiting the fibrotic response by genetic ablation of col1a2-expressing cells impaired cardiomyocyte proliferation. We conclude that ECM-producing cells are key players in the regenerative process and suggest that antifibrotic therapies might be less efficient than strategies targeting fibroblast inactivation.
Controller-to-ControllerCommunication and Coordination Taxonomy (C 4 T)

While previous research in the air traffic control (ATC) communications area has generally concentrated on controller-pilot communications, this program of research focuses on controller-to-controller communications. At the Air Route Traffic Control Center (ARTCC), teams of two controllers, R-side and D-side, are required to communicate on a continuing basis to coordinate the duties of their sector. As modernization of the ATC system progresses, questions arise concerning the effects these changes will have on intra-enroute sector team (EST) communications.In anticipation of technology changes, the Federal Aviation Administration commissioned a series of studies investigating intra-EST communication. This initial study details the design and subsequent field testing of the Controller-to-Controller Communication and Coordination Taxonomy (C 4 T). The taxonomy is designed to capture the following general communication categories: Topic, Format (grammatical form), and Expression. The final taxonomy resulting from this research contains 12 ATC topics (i.e., Traffic, Altitude, etc.). Communication Grammatical Format contained 5 subcategories: Question, Answer, Statement, Command, and Command Answer. Communication Expression
Bombesin Antagonists for Targeting Gastrin-Releasing Peptide Receptor-Positive Tumors : Design, Synthesis, Preclinical Evaluation and Optimization of Imaging Agents

IntroductionOverexpression of gastrin-releasing peptide receptors (GRPR) has been reported in several cancers. Bombesin (BN) analogs are short peptides with a high affinity for GRPR. Different BN analogs were evaluated for radionuclide imaging and therapy of GRPR-expressing tumors. We have previously investigated an antagonistic analog of BN (D-Phe-Gln-Trp-Ala-Val-Gly-His-Sta-Leu-NH2, RM26) conjugated to NOTA via a PEG2 spacer (NOTA-PEG2-RM26) labeled with 68Ga, 111In and Al18F. 68Ga-labeled NOTA-PEG2-RM26 showed high tumor-to-organ ratios.MethodsThe influence of different macrocyclic chelators (NOTA, NODAGA, DOTA and DOTAGA) on the targeting properties of 68Ga-labeled PEG2-RM26 was studied in vitro and in vivo.ResultsAll conjugates were labeled with generator-produced 68Ga with high yields and demonstrated high stability and specific binding to GRPR. The IC50 values of natGa-X-PEG2-RM26 (X = NOTA, DOTA, NODAGA, DOTAGA) were 2.3 ± 0.2, 3.0 ± 0.3, 2.9 ± 0.3 and 10.0 ± 0.6 nM, respectively. The internalization of the conjugates by PC-3 cells was low. However, the DOTA-conjugated analog demonstrated a higher internalization rate compared to other analogs. GRPR-specific uptake was found in receptor-positive normal tissues and PC-3 xenografts for all conjugates. The biodistribution of the conjugates was influenced by the choice of the chelator moiety. Although all radiotracers cleared rapidly from the blood, [68Ga]Ga-NOTA-PEG2-RM26 showed significantly lower uptake in lung, muscle and bone compared to the other analogs. The uptake in tumors (5.40 ± 1.04 %ID/g at 2 h p.i.) and the tumor-to-organ ratios (25 ± 3, 157 ± 23 and 39 ± 4 for blood, muscle and bone, respectively) were significantly higher for the NOTA-conjugate than the other analogs.ConclusionsChelators had a clear influence on the biodistribution and targeting properties of 68Ga-labeled antagonistic BN analogs. Positively charged [68Ga]Ga-NOTA-PEG2-RM26 provided a low kidney radioactivity uptake, high affinity, high tumor uptake and high image contrast.
Cytokines IL-17 and IL-22 in the host response to infection

Abstract Cytokines IL-17 and IL-22 play pivotal roles in host defense against microbes and in the development of chronic inflammatory diseases. These cytokines are produced by cells that are often located in epithelial barriers, including subsets of T cells and innate lymphoid cells. In general, IL-17 and IL-22 can be characterized as important cytokines in the rapid response to infectious agents, both by recruiting neutrophils and by inducing the production of antimicrobial peptides. Although each cytokine induces an innate immune response in epithelial cells, their functional spectra are generally distinct: IL-17 mainly induces an inflammatory tissue response and is involved in the pathogenesis of several autoimmune diseases, whereas IL-22 is largely protective and regenerative. In this review, we compare IL-17 and IL-22, describing overlaps and differences in their cellular sources as well as their regulation, signaling, biological functions and roles during disease, with a focus on the contribution of these cytokines to the gut mucosal barrier during bacterial infection.
The Potential of Integrating Provitamin A-Biofortified Maize in Smallholder Farming Systems to Reduce Malnourishment in South Africa

Biofortification interventions have the potential to combat malnutrition. This review explored the use of provitamin A-biofortified maize (PVABM) as a vitamin A deficiency (VAD) reduction agricultural-based strategy. Maize has been identified as one of the key staple crops for biofortification to reduce hidden hunger in Africa. Most nutrition interventions have not been successful in reducing hunger because rural communities, who mainly rely on agriculture, have been indirectly excluded. The biofortification intervention proposed here aims to be an inclusive strategy, based on smallholder farming systems. Vitamin A is a micronutrient essential for growth, immune function, reproduction and vision, and its deficiency results in VAD. VAD is estimated to affect more than 250 million children in developing countries. In Africa, especially sub-Saharan Africa, maize is a staple food for rural communities, consumed by most household members. Due to carotenoids, PVABM presents an orange color. This color has been reported to lead to negative perceptions about PVABM varieties. The perceived agronomic traits of this maize by smallholder farmers have not been explored. Adoption and utilization of PVABM varieties relies on both acceptable consumer attributes and agronomic traits, including nutritional value. It is therefore important to assess farmers’ perceptions of and willingness to adopt the varieties, and the potential markets for PVABM maize. It is essential to establish on-farm trials and experiments to evaluate the response of PVABM under different climatic conditions, fertilizer levels and soils, and its overall agronomic potential. For the better integration of PVABM with smallholder farming systems, farmer training and workshops about PVABM should be part of any intervention. A holistic approach would enhance farmers’ knowledge about PVABM varieties and that their benefits out-compete other existing maize varieties.
Energy-Efficient Data Collection Method for Sensor Networks by Integrating Asymmetric Communication and Wake-Up Radio

In large-scale wireless sensor networks (WSNs), nodes close to sink nodes consume energy more quickly than other nodes due to packet forwarding. A mobile sink is a good solution to this issue, although it causes two new problems to nodes: (i) overhead of updating routing information; and (ii) increased operating time due to aperiodic query. To solve these problems, this paper proposes an energy-efficient data collection method, Sink-based Centralized transmission Scheduling (SC-Sched), by integrating asymmetric communication and wake-up radio. Specifically, each node is equipped with a low-power wake-up receiver. The sink node determines transmission scheduling, and transmits a wake-up message using a large transmission power, directly activating a pair of nodes simultaneously which will communicate with a normal transmission power. This paper further investigates how to deal with frame loss caused by fading and how to mitigate the impact of the wake-up latency of communication modules. Simulation evaluations confirm that using multiple channels effectively reduces data collection time and SC-Sched works well with a mobile sink. Compared with the conventional duty-cycling method, SC-Sched greatly reduces total energy consumption and improves the network lifetime by 7.47 times in a WSN with 4 data collection points and 300 sensor nodes.
Quality in Development Process for Software Factories According to ISO 15504

Currently the concept of Software Factories (SF), where reuse plays a leading role, is being adopted. Due to the different approaches in this area, and although SF concept is not new in Software Engineering, it is still not mature enough to clearly identify the treatment of certain variables within the process. One of these variables is Quality. Therefore, this paper presents a historical review of the SF concept, proposes an ontology based on the most recent definitions and establishes a relationship between these concepts and the ISO 15504 standard, with the purpose of specifying the systemic quality in software developer companies that decide to implement an SF strategy.
The Emergence of Knowledge and How it Supports the Memory for Novel Related Information

Abstract Current theories suggest that memories for novel information and events, over time and with repeated retrieval, lose the association to their initial learning context. They are consolidated into a more stable form and transformed into semantic knowledge, that is, semanticized. Novel, related information can then be rapidly integrated into such knowledge, leading to superior memory. We tested these hypotheses in a longitudinal, 302‐day, human functional magnetic resonance imaging study in which participants first overlearned and consolidated associative structures. This phase was associated with a shift from hippocampal‐ to ventrolateral prefrontal cortex (vlPFC)‐mediated retrieval, consistent with semanticization. Next, participants encoded novel, related information whose encoding into the already acquired knowledge was orchestrated by the ventromedial prefrontal cortex. Novel related information exhibited reduced forgetting compared with novel control information, which corresponded to a faster shift from hippocampal‐ to vlPFC‐mediated retrieval. In sum, the current results suggest that memory for novel information can be enhanced by anchoring it to prior knowledge via acceleration of the processes observed during semanticization.
Analysis of Planning Poker Factors between University and Enterprise

The experience of professionals in software development companies is a major factor to estimate a User Story (US). Professionals have a different vision of problems because they have many years working on various projects. There are many variables to take into account while planning a US, so, students with little experience have problems to provide an accurate estimation due to the lack of an experts vision. It is necessary to identify student problems to help them to make a better decision. The objective of this study is to determine the engineering students view in estimating US through Planning Poker. We compared opinions from Scrum experts and students through the following factors: experience, time, effort, priority, and US's value. Results indicated similar opinions on most factors; however, the time factor had high contrast in opinions. Identifying these aspects and providing solutions or suggestions can be useful for students to join the software industry better prepared in regard of the estimation of USs.
Dictionary learning - from local towards global and adaptive

This paper studies the convergence behaviour of dictionary learning via the Iterative Thresholding and K-residual Means (ITKrM) algorithm. On one hand, it is proved that ITKrM is a contraction under much more relaxed conditions than previously necessary. On the other hand, it is shown that there seem to exist stable fixed points that do not correspond to the generating dictionary, which can be characterised as very coherent. Based on an analysis of the residuals using these bad dictionaries, replacing coherent atoms with carefully designed replacement candidates is proposed. In experiments on synthetic data, this outperforms random or no replacement and always leads to full dictionary recovery. Finally, the question how to learn dictionaries without knowledge of the correct dictionary size and sparsity level is addressed. Decoupling the replacement strategy of coherent or unused atoms into pruning and adding, and slowly carefully increasing the sparsity level, leads to an adaptive version of ITKrM. In several experiments, this adaptive dictionary learning algorithm is shown to recover a generating dictionary from randomly initialized dictionaries of various sizes on synthetic data and to learn meaningful dictionaries on image data.