Miracle-dz/UniFAR-FTUs huggingface dataset:
Pharmacometabolomics Informs Quantitative Radiomics for Glioblastoma Diagnostic Innovation

Applications of omics systems biology technologies have enormous promise for radiology and diagnostics in surgical fields. In this context, the emerging fields of radiomics (a systems scale approach to radiology using a host of technologies, including omics) and pharmacometabolomics (use of metabolomics for patient and disease stratification and guiding precision medicine) offer much synergy for diagnostic innovation in surgery, particularly in neurosurgery. This synthesis of omics fields and applications is timely because diagnostic accuracy in central nervous system tumors still challenges decision-making. Considering the vast heterogeneity in brain tumors, disease phenotypes, and interindividual variability in surgical and chemotherapy outcomes, we believe that diagnostic accuracy can be markedly improved by quantitative radiomics coupled to pharmacometabolomics and related health information technologies while optimizing economic costs of traditional diagnostics. In this expert review, we present an innovation analysis on a systems-level multi-omics approach toward diagnostic accuracy in central nervous system tumors. For this, we suggest that glioblastomas serve as a useful application paradigm. We performed a literature search on PubMed for articles published in English between 2006 and 2016. We used the search terms ‘‘radiomics,’’ ‘‘glioblastoma,’’ ‘‘biomarkers,’’ ‘‘pharmacogenomics,’’ ‘‘pharmacometabolomics,’’ ‘‘pharmacometabonomics/pharmacometabolomics,’’ ‘‘collaborative informatics,’’ and ‘‘precision medicine. ’’ A list of the top 4 insights we derived from this literature analysis is presented in this study. For example, we found that (i) tumor grading needs to be better refined, (ii) diagnostic precision should be improved, (iii) standardization in radiomics is lacking, and (iv) quantitative radiomics needs to prove clinical implementation. We conclude with an interdisciplinary call to the metabolomics, pharmacy/pharmacology, radiology, and surgery communities that pharmacometabolomics coupled to information technologies (chemoinformatics tools, databases, collaborative systems) can inform quantitative radiomics, thus translating Big Data and information growth to knowledge growth, rational drug development and diagnostics innovation for glioblastomas, and possibly in other brain tumors.
Protection against Tuberculosis with Homologous or Heterologous Protein/Vector Vaccine Approaches Is Not Dependent on CD8+ T Cells

Considerable effort has been directed to develop Mycobacterium tuberculosis vaccines to boost bacille Calmette-Guérin or for those who cannot be immunized with bacille Calmette-Guérin. We hypothesized that CD4+ and CD8+ T cell responses with a heterologous prime/boost vaccine approach could induce long-lived vaccine efficacy against M. tuberculosis in C57BL/6 mice. We produced an adenovirus vector expressing ID93 (Ad5-ID93) for induction of CD8 T cells to use with our candidate tuberculosis vaccine, ID93/glucopyranosyl lipid adjuvant (GLA)-stable emulsion (SE), which induces potent Th1 CD4 T cells. Ad5-ID93 generates ID93-specific CD8+ T cell responses and induces protection against M. tuberculosis. When Ad5-ID93 is administered in a prime-boost strategy with ID93/GLA-SE, both CD4+ and CD8+ T cells are generated and provide protection against M. tuberculosis. In a MHC class I–deficient mouse model, all groups including the Ad5-ID93 group elicited an Ag-specific CD4+ T cell response and significantly fewer Ag-specific CD8+ T cells, but were still protected against M. tuberculosis, suggesting that CD4+ Th1 T cells could compensate for the loss of CD8+ T cells. Lastly, the order of the heterologous immunizations was critical. Long-lived vaccine protection was observed only when Ad5-ID93 was given as the boost following an ID93/GLA-SE prime. The homologous ID93/GLA-SE prime/boost regimen also induced long-lived protection. One of the correlates of protection between these two approaches was an increase in the total number of ID93-specific IFN-γ–producing CD4+ T cells 6 mo following the last immunization. Our findings provide insight into the development of vaccines not only for tuberculosis, but other diseases requiring T cell immunity.
Design of parallel LDPC interleaver architecture: A bipartite edge coloring approach

Parallel hardware architecture proves to be an excellent compromise between area, cost, flexibility and high throughput in the hardware design of LDPC decoder. However, this type of architecture suffers from memory mapping problem: concurrent read and write accesses to data have to be performed at each time instance without any conflict. In this paper, we present an original approach based on the tanner graph modeling and a modified bipartite edge coloring algorithm to design parallel LDPC interleaver architecture.
Managing Hot Flushes with Group Cognitive Behaviour Therapy: An evidence-based treatment manual for health professionals

Fenlon, Foreword. Acknowledgements. Introduction. Session 1: Psychoeducation and the Cognitive Behavioural Model. Session 2: Stress Management, Improving Wellbeing and Identifying Precipitants. Session 3: Managing Hot Flushes Using a Cognitive Behavioural Approach. Session 4: Managing Night Sweats and Improving Sleep (Part One). Session 5: Managing Night Sweats and Sleep (Part Two). Session 6: Review and Maintaining Changes. Resources. References. Appendix: Handouts. Slides. Index
Diabetic Retinopathy detection using geometrical techniques related to the underlying physiology

A computer algorithm is developed using a set of geometrical measures of Diabetic Retinopathy on fundus images. The algorithm is extended from previous work with a focus on accurately ruling out false exudates that are calculated from an initial screening. Sensitivities and specificities are used to measure the effectiveness of maintaining accurate detection of exudates while avoiding false positives with respect to an initial set of possible exudates. A very high specificity of 98.4% and good sensitivity of 88.6% on 12 images shows the potential of the method. These results justify future clinical trials involving Ophthalmologists. An eye tracking procedure that could characterize what regions of the retina that experienced Ophthalmologists focus on is discussed.
Bosentan for sarcoidosis-associated pulmonary hypertension, age-adjusted D-dimer levels in pulmonary embolism, and mean arterial blood pressure targets in septic shock.

Pulmonary hypertension (PH) is present in a significant number of patients with advanced sarcoidosis, and is associated with increased mortality. Baughman and colleagues (1) performed a double-blind, randomized, placebo-controlled trial to determine whether bosentan is effective in treating sarcoidosis-associated PH. A total of 39 patients with sarcoidosis and pulmonary artery (PA) hypertension were randomized to receive either bosentan or placebo in a 2:1 ratio. Patients were excluded if they had severe exercise limitation (New York Heart Association class IV), severe airway obstruction, or significant heart failure. Right heart catheterization was performed before and after 16 weeks of therapy. Outcomes included the changes in mean PA pressure, 6-minute walk distance (6MWD), dyspnea, and quality of life as assessed by validated questionnaires. In the 30 patients with serial hemodynamic data, mean PA pressure decreased by 4 (66.6) mm Hg in the bosentan group (P , 0.02), and increased by 1 (63.7) mm Hg (P . 0.05) in the placebo group. There was no significant change in 6MWD, dyspnea, or quality of life scores in either group. Themajor limitation of this study is its emphasis on PA pressure. Changes in PA pressure correlate poorly with clinical outcomes. Contemporary studies of PH therapy generally emphasize functional outcomes, such as 6MWD (2). In this study, 6MWD decreased in the bosentan group (223 6 69.5 m; P . 0.05), whereas it increased in the placebo group (176 44.1; P. 0.05). Although not statistically significant, this difference, together with more frequent desaturation in the bosentan group, suggests that bosentan worsened gas exchange in some patients (3). In this study, 18 of 35 patients had fibrosis on chest radiograph, a forced vital capacity of less than 60%, or both. However, even a subgroup analysis of patients with forced vital capacity greater than 50% failed to demonstrate an increased 6MWD. Given the modest PH in this study (mean PA pressure, z35 mm Hg; mean right atrial pressure, 5 mm Hg), it is possible that patients with more severe PH (i.e., out of proportion to their fibrosis) would have experienced an increase in their exercise capacity. Until additional studies are performed, however, patients with sarcoidosis-associated PH should be referred to centers with expertise in PH and monitored closely for response to vasodilator therapy, if it is initiated (3). n
Surviving, thriving and being outside: applying the capabilities approach to reconceptualise the social justice experiences of people with mental distress

The empirical evidence associating people with mental distress and social injustice is unequivocal. This thesis offers a least reductive, structured qualitative exploration of how different social justice outcomes for people in this social group happen. To achieve this the study explores whether and how the capabilities approach can be applied to provide a normative means of explaining the social justice experiences of people with mental distress. It does this through conducting and analysing individual interviews with twenty-two people living in Glasgow who have recent in-patient experience of psychiatric hospital, sixteen participants being interviewed twice. The interviews are framed by combining concepts from the capabilities approach with relevant sociological literature, seeking to: understand the relationship between personal, social and structural factors affecting lived experiences; consider the character of social justice experienced and conceptualise this using concepts from the capabilities approach; take a critical realist approach to understanding how social justice experiences may be produced and reproduced; pursue these aims with regard to both values-based research principles from the survivor-influenced literature and participation principles from the capabilities approach. By critically interpreting empirical data using capabilities concepts and sociological concepts, the analysis is able to combine what had been two separate fields of study (Holmwood, 2013) and provide an original interpretation of how social injustice tends to be reproduced. The substantive findings explain how different social justice outcomes for people with mental distress are shaped by living with mental distress, experiencing the psychiatric system, and living in society. Although participants tend to have characteristics of ‘surviving’, or living with ongoing social injustice, a minority have characteristics of thriving. Some participants within both characteristic groups also experience ‘being outside’ dominant social norms. Methodologically the study demonstrates that concepts central to capabilities such as Conversion Factors and the domains approach can be operationalised to explain social justice outcomes for this social group, adding to and critiquing these concepts in the process. Theoretically, the thesis proposes a nascent critical capabilities model of mental distress, reinforcing the compatibility between the capabilities approach and critical realism, so providing a further contribution to the sociology of mental distress.
Evolution of Salmonella-Host Cell Interactions through a Dynamic Bacterial Genome

Salmonella Typhimurium has a broad arsenal of genes that are tightly regulated and coordinated to facilitate adaptation to the various host environments it colonizes. The genome of Salmonella Typhimurium has undergone multiple gene acquisition events and has accrued changes in non-coding DNA that have undergone selection by regulatory evolution. Together, at least 17 horizontally acquired pathogenicity islands (SPIs), prophage-associated genes, and changes in core genome regulation contribute to the virulence program of Salmonella. Here, we review the latest understanding of these elements and their contributions to pathogenesis, emphasizing the regulatory circuitry that controls niche-specific gene expression. In addition to an overview of the importance of SPI-1 and SPI-2 to host invasion and colonization, we describe the recently characterized contributions of other SPIs, including the antibacterial activity of SPI-6 and adhesion and invasion mediated by SPI-4. We further discuss how these fitness traits have been integrated into the regulatory circuitry of the bacterial cell through cis-regulatory evolution and by a careful balance of silencing and counter-silencing by regulatory proteins. Detailed understanding of regulatory evolution within Salmonella is uncovering novel aspects of infection biology that relate to host-pathogen interactions and evasion of host immunity.
Examining Evident Interdisciplinarity Among Prides of Lion Researchers

Lions (Panthera leo) have experienced dramatic population declines in recent decades and today, inhabit just a fraction of their historic range. The reasons behind these declines are many, but conflict with humans, principally motivated by lion depredation of livestock, is among the most influential. Recent calls within the scientific community have identified that wicked problems like these should be addressed using interdisciplinary approaches. Here we examined the extent to which human-lion conflict research has been interdisciplinary. We conducted an extensive review of the literature and uncovered 88 papers, published between 1990 and 2015, that assessed human-lion interaction and the ecology of lions exposed to anthropogenic disturbance. While human-lion conflict research experienced near-exponential growth across this time period, the number of co-authors engaged in this research changed very little (mean = 3.28, se = 0.19). Moreover, co-authors of this research tended to be affiliated with units from just three highly-related STEM disciplines (biology, wildlife management, and environmental science). Comparatively, co-authors affiliated with units in the humanities and social sciences occurred in <4% of all papers examined. Our analysis also presents a novel framework that positions human-lion conflict research as having five, not two dimensions, as has been commonly conceptualized. These dimensions include not only the human and the lion dimensions, but also the livestock, wild prey, and environmental dimensions. None of the papers that we evaluated concurrently studied all five of these dimensions to determine their impact on human-lion conflict. Furthermore, despite the fact that human-lion conflict research was primarily developed by co-authors from STEM disciplines, the most common dimension evaluated was the human dimension, requiring social science and humanities expertise. Our analysis indicates that interdisciplinarity among human-lion conflict research has historically been low. These low levels of interdisciplinarity observed from 1990-2015 however, are not representative of the ongoing efforts to develop more inclusive research teams to solve human-lion conflict. Thus, we discuss the implications of this research for the development of sustainable solutions to conserve lions and preserve human well-being and identify potential avenues forward to create more interdisciplinary prides of lion researchers.
Thyroid Cancer Study among Ukrainian Children Exposed to Radiation after the Chornobyl Accident: Improved Estimates of the Thyroid Doses to the Cohort Members

AbstractIn collaboration with the Ukrainian Research Center for Radiation Medicine, the U.S. National Cancer Institute initiated a cohort study of children and adolescents exposed to Chornobyl fallout in Ukraine to better understand the long-term health effects of exposure to radioactive iodines. All 13,204 cohort members were subjected to at least one direct thyroid measurement between 30 April and 30 June 1986 and resided at the time of the accident in the northern parts of Kyiv, Zhytomyr, or Chernihiv Oblasts, which were the most contaminated territories of Ukraine as a result of radioactive fallout from the Chornobyl accident. Thyroid doses for the cohort members, which had been estimated following the first round of interviews, were re-evaluated following the second round of interviews. The revised thyroid doses range from 0.35 mGy to 42 Gy, with 95% of the doses between 1 mGy and 4.2 Gy, an arithmetic mean of 0.65 Gy, and a geometric mean of 0.19 Gy. These means are 70% of the previous estimates, mainly because of the use of country-specific thyroid masses. Many of the individual thyroid dose estimates show substantial differences because of the use of an improved questionnaire for the second round of interviews. Limitations of the current set of thyroid dose estimates are discussed. For the epidemiologic study, the most notable improvement is a revised assessment of the uncertainties, as shared and unshared uncertainties in the parameter values were considered in the calculation of the 1,000 stochastic estimates of thyroid dose for each cohort member. This procedure makes it possible to perform a more realistic risk analysis.
Microarray studies on the genes responsive to the addition of spermidine or spermine to a Saccharomyces cerevisiae spermidine synthase mutant

The naturally occurring polyamines putrescine, spermidine or spermine are ubiquitous in all cells. Although polyamines have prominent regulatory roles in cell division and growth, precise molecular and cellular functions are not well‐established in vivo. In this work we have performed microarray experiments with a spermidine synthase, spermine oxidase mutant (Δspe3 Δfms1) strain to investigate the responsiveness of yeast genes to supplementation with spermidine or spermine. Expression analysis identified genes responsive to the addition of either excess spermidine (10−5 M) or spermine (10−5 M) compared to a control culture containing 10−8 M spermidine. 247 genes were upregulated > two‐fold and 11 genes were upregulated >10‐fold after spermidine addition. Functional categorization of the genes showed induction of transport‐related genes and genes involved in methionine, arginine, lysine, NAD and biotin biosynthesis. 268 genes were downregulated more than two‐fold, and six genes were downregulated > eight‐fold after spermidine addition. A majority of the downregulated genes are involved in nucleic acid metabolism and various stress responses. In contrast, only a few genes (18) were significantly responsive to spermine. Thus, results from global gene expression profiling demonstrate a more major role for spermidine in modulating gene expression in yeast than spermine. Copyright © 2009 John Wiley & Sons, Ltd.
HIV-1 Viral Subtype Differences in the Rate of CD4+ T-Cell Decline Among HIV Seroincident Antiretroviral Naive Persons in Rakai District, Uganda

Background:Data on the effect of HIV-1 viral subtype on CD4+ T-cell decline are limited. Methods:We assessed the rate of CD4+ T-cell decline per year among 312 HIV seroincident persons infected with different HIV-1 subtypes. Rates of CD4+ decline by HIV-1 subtype were determined by linear mixed effects models, using an unstructured convariance structure. Results:A total of 59.6% had D, 15.7% A, 18.9% recombinant viruses (R), and 5.8% multiple subtypes (M). For all subtypes combined, the overall rate of CD4+ T-cell decline was −34.5 [95% confidence interval (CI), −47.1, −22.0] cells/μL per yr, adjusted for age, sex, baseline CD4+ counts, and viral load. Compared with subtype A, the adjusted rate of CD4 cell loss was −73.7/μL/yr (95% CI, −113.5, −33.8, P < 0.001) for subtype D, −43.2/μL/yr (95% CI, −90.2, 3.8, P = 0.072) for recombinants, and −63.9/μL/yr (95% CI, −132.3, 4.4, P = 0.067) for infection with multiple HIV subtypes. Square-root transformation of CD4+ cell counts did not change the results. Conclusions:Infection with subtype D is associated with significantly faster rates of CD4+ T-cell loss than subtype A. This may explain the more rapid disease progression for subtype D compared with subtype A.
Sedentary Behavior Research Priorities--NHLBI/NIA Sedentary Behavior Workshop Summary.

Over the course of 2013, the National Heart, Lung and Blood Institute (NHLBI) and the National Institute on Aging (NIA) collaborated with a multi-national group of expert scientists to convene, host and facilitate a four-part virtual webinar workshop on sedentary behavior. Participants met to evaluate and discuss the current epidemiological, clinical and other relevant literature on sedentary behavior and to identify research priorities relative to preventing cardiovascular disease and mitigating aging-related disability and functional outcomes. The workshop was predicated on findings of insufficient levels of population adherence to current physical activity recommendations (1,12) and the need to address the NHLBI and NIA research portfolio gaps in the area of sedentary behavior.
Multi-Portfolio Optimization: A Potential Game Approach

In modern asset management, portfolio managers address the multi-account investment decision problem by optimizing each account's portfolio separately based on the trading requirements and portfolio constraints of the individual clients. However, trades associated with the individual accounts are usually pooled together for execution, therefore amplifying the level of the so-called market impact on all accounts. If this aggregate market impact is not considered when each account is individually optimized, the actual market impact can be severely under-estimated. Multi-portfolio optimization aims at finding the optimal rebalancing of the multiple accounts by considering their joint effects while adhering to account-specific constraints. In this paper, we first model this phenomenon as a Nash Equilibrium problem (NEP) and thereafter consider a generalized NEP (GNEP) for the case where there are global constraints imposed on all accounts, adopting as a desirable outcome the concept of Nash Equilibrium (NE). For both game problems, we give a complete characterization of the NE, including its existence and uniqueness, and devise various distributed algorithms with provable convergence. Interestingly, the proposed methodology heavily hinges on a number of well-known and important signal processing techniques.