Miracle-dz/UniFAR-FTUs huggingface dataset:
Tissue factor expressed by microparticles is associated with mortality but not with thrombosis in cancer patients

Summary A prothrombotic state is one of the hallmarks of malignancy and a major contributor to morbidity and mortality in cancer patients. Tissue factor (TF) is often overexpressed in malignancy and is a prime candidate in predicting the hypercoagulable state. Moreover, increased number of TF-exposing microparticles (MPs) in cancer patients may contribute to venous thromboembolism (VTE). We have conducted a prospective cohort study to determine whether elevated TF antigen, TF activity and TF associated to MPs (MPs-TF) are predictive of VTE and mortality in cancer patients. The studied population consisted of 252 cancer patients and 36 healthy controls. TF antigen and activity and MPs-TF were determined by ELISA and chromogenic assays. During a median follow-up of 10 months, 40 thrombotic events were recorded in 34 patients (13.5%), and 73 patients (28.9%) died. TF antigen and activity were significantly higher in patients than in controls (p<0.01) mainly in patients with advanced stages, whereas no differences were observed for TF activity of isolated MPs. We did not find a statistically significant association of TF variables with the risk of VTE. Multivariate analysis adjusting for age, sex, type of cancer and other confounding variables showed that TF activity (p<0.01) and MPs-TF activity (p<0.05) were independently associated with mortality. In conclusion, while TF variables were not associated with future VTE in cancer patients, we found a strong association of TF and MPs-TF activity with mortality, thus suggesting they might be good prognostic markers in cancer patients.
Molecular Evidence for a Uniform Microbial Community in Sponges from Different Oceans

ABSTRACT Sponges (class Porifera) are evolutionarily ancient metazoans that populate the tropical oceans in great abundances but also occur in temperate regions and even in freshwater. Sponges contain large numbers of bacteria that are embedded within the animal matrix. The phylogeny of these bacteria and the evolutionary age of the interaction are virtually unknown. In order to provide insights into the species richness of the microbial community of sponges, we performed a comprehensive diversity survey based on 190 sponge-derived 16S ribosomal DNA (rDNA) sequences. The sponges Aplysina aerophoba and Theonella swinhoei were chosen for construction of the bacterial 16S rDNA library because they are taxonomically distantly related and they populate nonoverlapping geographic regions. In both sponges, a uniform microbial community was discovered whose phylogenetic signature is distinctly different from that of marine plankton or marine sediments. Altogether 14 monophyletic, sponge-specific sequence clusters were identified that belong to at least seven different bacterial divisions. By definition, the sequences of each cluster are more closely related to each other than to a sequence from nonsponge sources. These monophyletic clusters comprise 70% of all publicly available sponge-derived 16S rDNA sequences, reflecting the generality of the observed phenomenon. This shared microbial fraction represents the smallest common denominator of the sponges investigated in this study. Bacteria that are exclusively found in certain host species or that occur only transiently would have been missed. A picture emerges where sponges can be viewed as highly concentrated reservoirs of so far uncultured and elusive marine microorganisms.
Blockade of S100A8 and S100A9 Suppresses Neutrophil Migration in Response to Lipopolysaccharide 1

Recently, proinflammatory activities had been described for S100A8 and S100A9, two proteins found at inflammatory sites and within the neutrophil cytoplasm. In this study, we investigated the role of these proteins in neutrophil migration in vivo in response to LPS. LPS was injected into the murine air pouch, which led to the release of S100A8, S100A9, and S100A8/A9 in the pouch exudates that preceded accumulation of neutrophils. Passive immunization against S100A8 and S100A9 led to a 52% inhibition of neutrophil migration in response to LPS at 3 h postinjection. Injection of LPS was also associated with an increase in peripheral blood neutrophils and the presence in serum of S100A9 and S100A8/A9. Intravenous injection of S100A8, S100A9, or S100A8/A9 augmented the number of circulating neutrophils and diminished the number of neutrophils in the bone marrow, demonstrating that S100A8 and S100A9 induced the mobilization of neutrophils from the bone marrow to the blood. Finally, passive immunization with anti-S100A9 inhibited the neutrophilia associated with LPS injection in the air pouch. These results suggest that S100A8 and S100A9 play a role in the inflammatory response to LPS by inducing the release of neutrophils from the bone marrow and directing their migration to the inflammatory site.
Person Re-identification for Improved Multi-person Multi-camera Tracking by Continuous Entity Association

We present a novel approach to person tracking within the context of entity association. In large-scale distributed multi-camera systems, person re-identification is a challenging computer vision task as the problem is two-fold: detecting entities through identification and recognition techniques; and connecting entities temporally by associating them in often crowded environments. Since tracking essentially involves linking detections, we can reformulate it purely as a re-identification task. The inherent advantage of such a reformulation lies in the ability of the tracking algorithm to effectively handle temporal discontinuities in multi-camera environments. To accomplish this, we model human appearance, face biometric and location constraints across cameras. We do not make restrictive assumptions such as number of people in a scene. Our approach is validated by using a simple and efficient inference algorithm. Results on two publicly available datasets, CamNeT and DukeMTMC, are significantly better compared to other existing methods.
Alcohol extracts of Echinacea inhibit production of nitric oxide and tumor necrosis factor-alpha by macrophages in vitro

Abstract It has been suggested that Echinacea has anti-inflammatory activity in vivo. Nitric oxide (NO), tumor necrosis factor-alpha (TNF-α), and interleukin-1beta are important mediators in the inflammatory response. The effect of alcohol extracts of E. angustifolia (EA), E. pallida (EPA) and E. purpurea (EP) on the production of these inflammatory mediators in both LPS-stimulated RAW 264.7 macrophages in vitro and murine peritoneal exudate cells (PECs) in vivo were investigated. As macrophages produce these inflammatory mediators in response to pathogenic infection, parallel cultures of macrophages were studied for phagocytosis and intracellular killing of Salmonella enterica. EPA and EP in vitro inhibited NO production and TNF-α release in a dose-dependent manner. RAW 264.7 cells treated with EA or EP showed decreased killing over 24 h, although EA enhanced bacterial phagocytosis. Upon bacterial infection, RAW 264.7 cells produce high levels of NO; however, an Echinacea-mediated decrease in NO production was observed. Echinacea alcohol extracts administered orally at 130 mg/kg per day for seven days had a weak effect on NO production and phagocytosis by LPS-stimulated PECs. The results indicated that all Echinacea species significantly decreased inflammatory mediators in vitro, however, only EA and EP reduced bacterial killing. Oral administration of Echinacea alcohol extracts did not adversely affect the development and anti-bacterial function of inflammatory PECs in vivo, however, NO production was decreased during bacterial infection of PECs.
Medical education: hitting the target but missing the point

Abstract There are dangers that a target-driven culture could be affecting medical education. In continuous professional development, many accreditation authorities require physicians to complete a fixed number of hours of continuous professional development per year or to acquire a certain amount of continuous professional development points per year. However, all these numbers are arbitrary and worse reinforce the message to physicians that it is time spent on learning that is important. In fact far more important than hours spent is the ability to assess learning needs, learn in the light of these needs and put learning into action. Targets have also started to come to the fore is in undergraduate and postgraduate training programmes, and in certain clinical topics such as dementia and in workforce development. Targets in any walk of life should be SMART – that is specific, measurable, achievable, realistic and time limited. However, not all targets in medical education satisfy these criteria of good-quality targets. There is also the wider question as to whether there is a good fit between medical education – which is largely a qualitative activity - and educational targets – which by their nature must be quantitative. Put simply, targets may not fit with education.
Structure of an N276-Dependent HIV-1 Neutralizing Antibody Targeting a Rare V5 Glycan Hole Adjacent to the CD4 Binding Site

ABSTRACT All HIV-1-infected individuals develop strain-specific neutralizing antibodies to their infecting virus, which in some cases mature into broadly neutralizing antibodies. Defining the epitopes of strain-specific antibodies that overlap conserved sites of vulnerability might provide mechanistic insights into how broadly neutralizing antibodies arise. We previously described an HIV-1 clade C-infected donor, CAP257, who developed broadly neutralizing plasma antibodies targeting an N276 glycan-dependent epitope in the CD4 binding site. The initial CD4 binding site response potently neutralized the heterologous tier 2 clade B viral strain RHPA, which was used to design resurfaced gp120 antigens for single-B-cell sorting. Here we report the isolation and structural characterization of CAP257-RH1, an N276 glycan-dependent CD4 binding site antibody representative of the early CD4 binding site plasma response in donor CAP257. The cocrystal structure of CAP257-RH1 bound to RHPA gp120 revealed critical interactions with the N276 glycan, loop D, and V5, but not with aspartic acid 368, similarly to HJ16 and 179NC75. The CAP257-RH1 monoclonal antibody was derived from the immunoglobulin-variable IGHV3-33 and IGLV3-10 genes and neutralized RHPA but not the transmitted/founder virus from donor CAP257. Its narrow neutralization breadth was attributed to a binding angle that was incompatible with glycosylated V5 loops present in almost all HIV-1 strains, including the CAP257 transmitted/founder virus. Deep sequencing of autologous CAP257 viruses, however, revealed minority variants early in infection that lacked V5 glycans. These glycan-free V5 loops are unusual holes in the glycan shield that may have been necessary for initiating this N276 glycan-dependent CD4 binding site B-cell lineage. IMPORTANCE The conserved CD4 binding site on gp120 is a major target for HIV-1 vaccine design, but key events in the elicitation and maturation of different antibody lineages to this site remain elusive. Studies have shown that strain-specific antibodies can evolve into broadly neutralizing antibodies or in some cases act as helper lineages. Therefore, characterizing the epitopes of strain-specific antibodies may help to inform the design of HIV-1 immunogens to elicit broadly neutralizing antibodies. In this study, we isolate a narrowly neutralizing N276 glycan-dependent antibody and use X-ray crystallography and viral deep sequencing to describe how gp120 lacking glycans in V5 might have elicited these early glycan-dependent CD4 binding site antibodies. These data highlight how glycan holes can play a role in the elicitation of B-cell lineages targeting the CD4 binding site.
CC‐chemokine class inhibition attenuates pathological angiogenesis while preserving physiological angiogenesis

Increasing evidence shows that CC‐chemokines promote inflammatory‐driven angiogenesis, with little to no effect on hypoxia‐mediated angiogenesis. Inhibition of the CC‐chemokine class may therefore affect angiogenesis differently depending on the pathophysiological context. We compared the effect of CC‐chemokine inhibition in inflammatory and physiological conditions. In vitro, the broad‐spectrum CC‐chemokine inhibitor “35K” inhibited inflammatory‐induced endothelial cell proliferation, migration, and tubulogenesis, with more modest effects in hypoxia. In vivo, adenoviruses were used to overexpress 35K (Ad35K) and GFP (AdGFP, control virus). Plasma chemokine activity was suppressed by Ad35K in both models. In the periarterial femoral cuff model of inflammatory‐driven angiogenesis, overexpression of 35K inhibited adventitial neovessel formation compared with control AdGFP‐infused mice. In contrast, 35K preserved neovascularization in the hindlimb ischemia model and had no effect on physiological neovascularization in the chick chorioallantoic membrane assay. Mechanistically, 2 key angiogenic proteins (VEGF and hypoxia‐inducible factor‐1α) were conditionally regulated by 35K, such that expression was inhibited in inflammation but was unchanged in hypoxia. In conclusion, CC‐chemokine inhibition by 35K suppresses inflammatory‐driven angiogenesis while preserving physiological ischemia‐mediated angiogenesis via conditional regulation of VEGF and hypoxia‐inducible factor‐1α. CC‐chemokine inhibition may be an alternative therapeutic strategy for suppressing diseases associated with inflammatory angiogenesis without inducing the side effects caused by global inhibition. —Ridiandries, A. , Tan, J. T. M. , Ravindran, D. , Williams, H. , Medbury, H. J., Lindsay, L. , Hawkins, C. , Prosser, H. C. G. , Bursill, C. A. CC‐chemokineclass inhibition attenuates pathological angiogenesis while preserving physiological angiogenesis. FASEB J. 31, 1179–1192 (2017). www.fasebj. org
Emotional eating and eating psychopathology in nonclinical groups: a cross-cultural comparison of women in Japan and the United Kingdom.

OBJECTIVE Emotional eating is associated with eating psychopathology among Western populations. It is not known whether the same conclusions hold in non-Western cultures, where norms for emotional expression differ. This study examined whether emotional eating has the same eating psychopathology correlates in different cultures. METHOD Three groups of nonclinical women were compared-Japanese living in Japan; Japanese living in the United Kingdom; and British living in the United Kingdom. They completed an Emotional Eating Scale and the Eating Disorders Inventory. RESULTS There were different patterns of association between emotional eating and eating attitudes in the three groups. British women showed a strong linkage, Japanese women living in Japan showed no association, and Japanese women in the United Kingdom showed an intermediate pattern. CONCLUSIONS Emotional eating may be less of an index of eating psychopathology in non-Western cultures. However, there appears to be an acculturative process, linking the two when one enters a Western culture. This cross-cultural difference may have implications for the targeting of therapies, although this conclusion requires support from further research.
A postsynaptic negative feedback mediated by coupling between AMPA receptors and Na+‐activated K+ channels in spinal cord neurones

Na+‐activated K+ channels (KNa) exist in different types of neurones and their activation has been shown to depend on Na+ influx via voltage‐activated channels. However, one major route for Na+ influx into neurones is through ionotropic receptors and its role in activating KNa is still unclear. We have examined whether Na+ influx induced by activation of AMPA receptors can activate KNa in lamprey spinal cord neurones. Our results showed that the application of AMPA induced not only the characteristic inward current but also produced an outward current outlasting the activation of the receptors. This outward current was mediated by K+ and was abolished when Na+ was substituted with Li+. The AMPA‐mediated KNa current was completely blocked by quinidine but was not modulated by increased intracellular Cl– concentration or ATP. Thus, Na+ influx via AMPA receptor channels activates KNa with properties similar to Slack channels. The AMPA‐activated KNa may act as an inherent negative feedback mechanism to regulate the homeostasis of excitation.
Including information about co-morbidity in estimates of disease burden: results from the World Health Organization World Mental Health Surveys

Background The methodology commonly used to estimate disease burden, featuring ratings of severity of individual conditions, has been criticized for ignoring co-morbidity. A methodology that addresses this problem is proposed and illustrated here with data from the World Health Organization World Mental Health Surveys. Although the analysis is based on self-reports about one's own conditions in a community survey, the logic applies equally well to analysis of hypothetical vignettes describing co-morbid condition profiles. Method Face-to-face interviews in 13 countries (six developing, nine developed; n=31 067; response rate=69.6%) assessed 10 classes of chronic physical and nine of mental conditions. A visual analog scale (VAS) was used to assess overall perceived health. Multiple regression analysis with interactions for co-morbidity was used to estimate associations of conditions with VAS. Simulation was used to estimate condition-specific effects. Results The best-fitting model included condition main effects and interactions of types by numbers of conditions. Neurological conditions, insomnia and major depression were rated most severe. Adjustment for co-morbidity reduced condition-specific estimates with substantial between-condition variation (0.24–0.70 ratios of condition-specific estimates with and without adjustment for co-morbidity). The societal-level burden rankings were quite different from the individual-level rankings, with the highest societal-level rankings associated with conditions having high prevalence rather than high individual-level severity. Conclusions Plausible estimates of disorder-specific effects on VAS can be obtained using methods that adjust for co-morbidity. These adjustments substantially influence condition-specific ratings.
Event‐Related desynchronization to contingent negative variation and Self‐Paced movement paradigms in Parkinson's disease

The event‐related desynchronization (ERD) to voluntary movemtnt is an indicator of cortical activation with a high time resolution and a specific spatial representation. We have evaluated 10 patients affected by Parkinson's disease (PD), free from L‐dopa treatment for at least 12 hours, and 10 control subjects. Each subject underwent ERD examination during self‐paced movement (SPM) and during contingent negative variation (CNV) paradigms. ERD was measured as the percentage decrease of alpha band power and calculated for frequency bands of 1 Hz, ranging between 8 and 12 Hz. For group comparisons, the frequency showing the highest ERD was selected for each subject and for each side. In the control group. ERD in the CNV paradigm began over the contralateral centroparietal electrodes 1475 ms before movement onset of the right hand and 1375 ms for the left. In the SPM paradigm, ERD started over the contralateral central electrodes 2150 ms and 1775 ms before movement onset of the right and left hand, respectively. In the PD group, ERD started over the contralateral central areas 800 ms and 475 ms before movement onset of the right and left hand, respectively, for CNV paradigm and 1200 ms and 750 ms for the right and left hand, respectively, for SPM paradigm. Therefore, contralateral ERD began closer to movement onset in PD compared with the control group in both paradigms. ERD over the sensorimotor areas ipsilateral to the movement was not significantly different in PD compared with the control group. The finding of delayed contralateral ERD in PD is according to the view that functional cortical activation related to movement preparation is impaired in PD. The lack of group differences in the onset of ipsilateral ERD, which appears close to movement execution than contralateral ERD both in normal subjects and in PD, suggests that different mechanisms may be involved in generating ERD over the hemispheres ipsilateral and contralateral to the movement, and that only the latter are impaired in PD.
ATP Generation in the Trypanosoma brucei Procyclic Form

Trypanosoma brucei is a parasitic protist responsible for sleeping sickness in humans. The procyclic form of this parasite, transmitted by tsetse flies, is considered to be dependent on oxidative phosphorylation for ATP production. Indeed, its respiration was 55% inhibited by oligomycin, which is the most specific inhibitor of the mitochondrial F0/F1-ATP synthase. However, a 10-fold excess of this compound did not significantly affect the intracellular ATP concentration and the doubling time of the parasite was only 1.5-fold increased, suggesting that oxidative phosphorylation is not essential for procyclic trypanosomes. To further investigate the sites of ATP production, we studied the role of two ATP producing enzymes, which are involved in the synthesis of pyruvate from phosphoenolpyruvate: the glycosomal pyruvate phosphate dikinase (PPDK) and the cytosolic pyruvate kinase (PYK). The parasite was not affected by PPDK gene knockout. In contrast, inhibition of PYK expression by RNA interference was lethal for these cells. In the absence of PYK activity, the intracellular ATP concentration was reduced by up to 2.3-fold, whereas the intracellular pyruvate concentration was not reduced. Furthermore, we show that this mutant cell line still excreted acetate from d-glucose metabolism, and both the wild type and mutant cell lines consumed pyruvate present in the growth medium with similar high rates, indicating that in the absence of PYK activity pyruvate is still present in the trypanosomes. We conclude that PYK is essential because of its ATP production, which implies that the cytosolic substrate level phosphorylation is essential for the growth of procyclic trypanosomes.
Assessment of DNA Damage in Leukoplakia Patients with Different Degrees of Dysplasia.

BACKGROUND Single cell gel electrophoresis (SCGE) assay also known as comet assay is a rapid and highly sensitive fluorescent molecular technique for detecting various forms of deoxyribonucleic acid (DNA) damage at individual cellular level. MATERIALS AND METHODS The present study was done to detect the extent of DNA damage in oral leukoplakia (OL) and compare with normal individuals. The sample population was obtained from an outpatient clinic of a tertiary teaching dental institute. A total of 36 consecutive patients with leukoplakia and 10 healthy normal volunteers were recruited for the study and assessed for the extent of DNA damage using SCGE following clinical diagnosis and histological grading. Peripheral blood was obtained by venipuncture and SCGE assay was performed. Mean comet tail length was recorded and analyzed statistically to compare the extent of damage in each group. RESULTS The mean comet tail length seen in leukoplakia patients with moderate to severe dysplasia was 1.25 ± 0.14 mm while for the control subjects, it was 0.31 ± 0.10 mm. The difference was statistically significant (p = 0.000). On comparing within the grades of leukoplakia, a progressive trend of increasing tail length was observed with increasing grades of dysplasia. CONCLUSION Deoxyribonucleic acid damage as measured by SCGE is seen in leukoplakia. A stepwise increase in DNA damage levels from healthy controls, through patients with non-dysplastic epithelium to varying grades of dysplasia has been observed indicating the extent of DNA damage in this high risk group.