Research prioritization through prediction of future impact on biomedical science: A position paper on inference-analytics

Background: Advances in biotechnology have created "big-data" situations in molecular and cellular biology. Several sophisticated algorithms have been developed that process big data to generate hundreds of biomedical hypotheses (or predictions). The bottleneck to translating this large number of biological hypotheses is that each of them needs to be studied by experimentation for interpreting its functional significance. Even when the predictions are estimated to be very accurate, from a biologist's perspective, the choice of which of these predictions is to be studied further is made based on factors like availability of reagents and resources and the possibility of formulating some reasonable hypothesis about its biological relevance. When viewed from a global perspective, say from that of a federal funding agency, ideally the choice of which prediction should be studied would be made based on which of them can make the most translational impact. Results: We propose that algorithms be developed to identify which of the computationally generated hypotheses have potential for high translational impact; this way, funding agencies and scientific community can invest resources and drive the research based on a global view of biomedical impact without being deterred by local view of feasibility. In short, data-analytic algorithms analyze big-data and generate hypotheses; in contrast, the proposed inference-analytic algorithms analyze these hypotheses and rank them by predicted biological impact. We demonstrate this through the development of an algorithm to predict biomedical impact of protein-protein interactions (PPIs) which is estimated by the number of future publications that cite the paper which originally reported the PPI. Conclusions: This position paper describes a new computational problem that is relevant in the era of big-data and discusses the challenges that exist in studying this problem, highlighting the need for the scientific community to engage in this line of research. The proposed class of algorithms, namely inference-analytic algorithms, is necessary to ensure that resources are invested in translating those computational outcomes that promise maximum biological impact. Application of this concept to predict biomedical impact of PPIs illustrates not only the concept, but also the challenges in designing these algorithms

Succinyl-CoA:3-ketoacid coenzyme A transferase (SCOT): development of an antibody to human SCOT and diagnostic use in hereditary SCOT deficiency

AbstractSuccinyl-CoA:3-ketoacid CoA transferase (SCOT) is a key enzyme for ketone body utilization. Hereditary SCOT deficiency in humans (McKusick catalogue number 245050) is characterized by intermittent ketoacidotic attacks and permanent hyperketonemia. Since previously-available antibody to rat SCOT did not crossreact with human SCOT, we developed an antibody against recombinant human SCOT expressed in a bacterial system. The recombinant SCOT was insoluble except under denaturing conditions. Antibody raised to this polypeptide recognized denatured SCOT and proved useful for immunoblot analysis. On immunoblots, SCOT was easily detectable in control fibroblasts and lymphocytes but was detected neither in fibroblast extracts from four SCOT-deficient patients, nor in lymphocytes from two SCOT-deficient patients. These data indicate that immunoblot analysis is useful for diagnosis of SCOT deficiency in combination with enzyme assay

Psychosocial interventions for people with dementia: a synthesis of systematic reviews

Objectives: Over the last 10 years there has been a multitude of studies of psychosocial interventions for people with dementia. However, clinical services face a dilemma about which intervention should be introduced into clinical practice because of the inconsistency in some of the findings between different studies and the differences in the study qualities and trustworthiness of evidence. There was a need to provide a comprehensive summary of the best evidence to illustrate what works. Methods: A review of the systematic reviews of psychosocial interventions in dementia published between January 2010 and February 2016 was conducted. Results: Twenty-two reviews (8 physical, 7 cognitive, 1 physical/cognitive and 6 other psychosocial interventions) with a total of 197 unique studies met the inclusion criteria. Both medium to longer-term multi-component exercise of moderate to high intensity, and, group cognitive stimulation consistently show benefits. There is not sufficient evidence to determine whether psychological or social interventions might improve either mood or behaviour due to the heterogeneity of the studies and interventions included in the reviews. Conclusion: There is good evidence that multi-component exercise with sufficient intensity improves global physical and cognitive functions and activities of daily living skills. There is also good evidence that group based cognitive stimulation improves cognitive functions, social interaction and quality of life. This synthesis also highlights the potential importance of group activities to improve social integration for people with dementia. Future research should investigate longer-term specific outcomes, consider the severity and types of dementia, and investigate mechanisms of change

A case of coexisting Warthin tumor and langerhans cell histiocytosis associated with necrosis, eosinophilic abscesses and a granulomatous reaction in intraparotid lymph nodes

We present a patient (50-year-old male) with coexisting Warthin tumor and involvement of two intraparotid lymph nodes by Langerhans cell histiocytosis associated with necrosis, eosinophilic abscesses and a granulomatous reaction. This is the second documented case of this unusual combination of histological changes in nodal Langerhans cell histiocytosis and the first case involving intraparotid lymph nodes occurring together with an ipsilateral Warthin tumor

Search for dinucleon decay into pions at Super-Kamiokande

A search for dinucleon decay into pions with the Super-Kamiokande detector has been performed with an exposure of 282.1 kiloton-years. Dinucleon decay is a process that violates baryon number by two units. We present the first search for dinucleon decay to pions in a large water Cherenkov detector. The modes $^{16}$O$(pp) \rightarrow$ $^{14}$C$\pi^{+}\pi^{+}$, $^{16}$O$(pn) \rightarrow$ $^{14}$N$\pi^{+}\pi^{0}$, and $^{16}$O$(nn) \rightarrow$ $^{14}$O$\pi^{0}\pi^{0}$ are investigated. No significant excess in the Super-Kamiokande data has been found, so a lower limit on the lifetime of the process per oxygen nucleus is determined. These limits are: $\tau_{pp\rightarrow\pi^{+}\pi^{+}} > 7.22 \times 10^{31}$ years, $\tau_{pn\rightarrow\pi^{+}\pi^{0}} > 1.70 \times 10^{32}$ years, and $\tau_{nn\rightarrow\pi^{0}\pi^{0}} > 4.04 \times 10^{32}$ years. The lower limits on each mode are about two orders of magnitude better than previous limits from searches for dinucleon decay in iron.Comment: 20 pages, 17 figures. Accepted for publication in Physical Review D on March 30, 201

Up-regulation of chemokine C-C ligand 2 (CCL2) and C-X-C chemokine 8 (CXCL8) expression by monocytes in chronic idiopathic urticaria

The disturbed cytokinechemokine network could play an important role in the onset of diseases with inflammatory processes such as chronic idiopathic urticaria (CIU). Our main objectives were to evaluate the relation between proinflammatory chemokine serum levels from CIU patients and their response to autologous skin test (ASST) and basophil histamine release (BHR). We also aimed to assess the chemokine secretion by peripheral blood mononuclear cells (PBMC) upon polyclonal stimulus and to evaluate chemokine CC ligand 2/C-X-C chemokine 8 (CCL2/CXCL8) and Toll-like receptor-4 (TLR-4) expression in monocytes. We observed significantly higher serum levels of the CXCL8, CXCL9, CXCL10 and CCL2 in CIU patients compared to the healthy group, regardless of the BHR or ASST response. The basal secretion of CCL2 by PBMC or induced by Staphylococcus aureus enterotoxin A (SEA) was higher in CIU patients than in the control group, as well as for CXCL8 and CCL5 secretions upon phytohaemagglutinin stimulation. Also, up-regulation of CCL2 and CXCL8 mRNA expression was found in monocytes of patients upon SEA stimulation. The findings showed a high responsiveness of monocytes through CCL2/CXCL8 expression, contributing to the creation of a proinflammatory environment in CIU.FAPESP [2007/58485-9]FAPESP[LIM-56/HCFMUSP