julilili42/papers huggingface dataset:
Long-lasting Disease Stabilization in the Absence of Toxicity in Metastatic Lung Cancer Patients Vaccinated with an Epitope Derived from Indoleamine 2,3 Dioxygenase
2013-11-12

Abstract Purpose: To investigate targeting of indoleamine 2,3 dioxygenase (IDO) enzyme using a synthetic peptide vaccine administered to patients with metastatic non–small cell lung cancer (NSCLC). Experimental Design: In a clinical phase I study, we treated 15 HLA-A2–positive patients with stage III–IV NSCLC in disease stabilization after standard chemotherapy. Patients were treated with imiquimod ointment and subcutaneous vaccinations (100 μg IDO5 peptide, sequence ALLEIASCL, formulated in 900 μL Montanide). Primary endpoint was toxicity. Clinical benefit and immunity were assessed as secondary endpoints. Results: No severe toxicity was observed. One patient developed a partial response (PR) after one year of vaccine treatment, whereas long-lasting stable disease (SD) ≥ 8.5 months was demonstrated in another six patients. The median overall survival (OS) was 25.9 months. Patients demonstrated significant improved OS (P = 0.03) when compared with the group of patients excluded because of HLA-A2 negativity. IDO-specific CD8+ T-cell immunity was demonstrated by IFN-γ Elispot and Tetramer staining. Fluorescence-activated cell sorting analyses demonstrated a significant reduction of the Treg population (P = 0.03) after the sixth vaccine (2.5 months) compared with pretreatment levels. Furthermore, expression of IDO was detected in nine of ten tumor biopsies by immunohistochemistry. High-performance liquid chromatography analyses of kynurenine/tryptophan (Kyn/Trp) ratio in sera were performed. In long-term analyses of two clinical responding patients, the ratio of Kyn/Trp remained stable. Conclusions: The vaccine was well tolerated with no severe toxicity occurring. A median OS of 25.9 months was demonstrated and long-lasting PR+SD was seen in 47% of the patients. Clin Cancer Res; 20(1); 221–32. ©2013 AACR.
Long-term remission and recurrence rates after first and second transsphenoidal surgery for Cushing's disease: care reality in the Munich Metropolitan Region
2013-11-12

Objective Transsphenoidal surgery (TSS) presents the treatment of choice for Cushing's disease (CD). Remission and recurrence rates vary dependent on tumor size, extension, adenoma visibility on magnetic resonance imaging, and neurosurgical expertise. Other than published from single-surgeon neurosurgical series so far, we have aimed to describe long-term remission and recurrence rates of CD in a series incorporating different neurosurgeons, trying to reflect care reality in the Munich Metropolitan Region, which is accommodated by three tertiary university and multiple, smaller neurosurgical centers. Design We conducted a retrospective analysis of 120 patients who underwent first and 36 patients who underwent second TSS as treatment for CD between 1990 and 2012. Methods Patients were divided into three groups according to remission status. Potential risk factors for recurrence, pituitary function, and strategy in persistent disease were assessed. Results Three outcome groups were identified according to remission status after first TSS (mean follow-up 79 months): remission, 71% (85/120), disease persistence, 29% (35/120), and disease recurrence, 34% (29/85) (mean time to recurrence 54 months). After second TSS ( n =36, mean follow-up 62 months), we documented remission in 42% (15/36), disease persistence in 58% (21/36), and disease recurrence in 40% (6/15) (mean time to recurrence 42 months). Postoperative hypocortisolism after first, though not after second, TSS was associated with a lower risk of suffering disease recurrence (risk=0.72; 95% CI 0.60–0.88; exact significance (two-sided) P =0.035). Conclusions Our study shows higher recurrence rates of CD after first TSS than previously reported. Second TSS leads an additional 8% of the patients to long-term CD remission.
Ablation of SGK1 Impairs Endothelial Cell Migration and Tube Formation Leading to Decreased Neo-Angiogenesis Following Myocardial Infarction
2013-11-12

Serum and glucocorticoid inducible kinase 1 (SGK1) plays a pivotal role in early angiogenesis during embryonic development. In this study, we sought to define the SGK1 downstream signalling pathways in the adult heart and to elucidate their role in cardiac neo-angiogenesis and wound healing after myocardial ischemia. To this end, we employed a viable SGK1 knockout mouse model generated in a 129/SvJ background. Ablation of SGK1 in these mice caused a significant decrease in phosphorylation of SGK1 target protein NDRG1, which correlated with alterations in NF-κB signalling and expression of its downstream target protein, VEGF-A. Disruption of these signalling pathways was accompanied by smaller heart and body size. Moreover, the lack of SGK1 led to defective endothelial cell (ECs) migration and tube formation in vitro, and increased scarring with decreased angiogenesis in vivo after myocardial infarct. This study underscores the importance of SGK1 signalling in cardiac neo-angiogenesis and wound healing after an ischemic insult in vivo.
Feasibility of Telaprevir-Based Triple Therapy in Liver Transplant Patients with Hepatitis C Virus: SVR 24 Results
2013-11-12

Management of recurrent Hepatitis C virus (HCV) infection following liver transplantation remains a major challenge. In non-transplanted HCV genotype 1 patients, the introduction of protease inhibitor-based regimens has significantly increased the rate of sustained virological response. In this follow-up study, on the first published cohort of post-liver transplant patients treated with telaprevir-based triple therapy, we investigated both efficacy and safety data in follow-up to 24 weeks (SVR 24) after end of treatment (EOT). SVR 24 efficacy and safety data from 9 liver transplant HCV patients being treated with telaprevir, pegylated interferon, and ribavirin, showed 5 of the transplanted patients accomplished the full duration of the 48 week triple therapy. Notable were the 4 patients found to be HCV RNA-negative at week 4, and 8 patients at week 12. Upon EOT, at week 48, 6 patients were HCV RNA-negative. Importantly, at follow-up (24 weeks after EOT), a favorable sustained virological response rate was observed in 5 of these patients with HCV RNA remaining negative, including in one patient who discontinued treatment prematurely. Due to side effects, 2 patients discontinued, 2 suffered from virological breakthrough after the telaprevir treatment phase, and 1 patient had a relapse after EOT. Two thirds of patients exhibited hematological side effects requiring ribavirin dose reductions, administration of erythropoetin, or even blood transfusions. This retrospective analysis provides evidence that--with respect to SVR 24--liver transplant patients suffering from HCV genotype 1 recurrence may benefit from a telaprevir-based triple therapy as this new regimen showed acceptable antiviral efficacy in this small cohort of mostly pre-treated patients. Management of drug-drug interactions is challenging, but feasible. In part severe side effects are frequent during treatment and require therapeutic interventions.
Synthesis and Characterization of the First Tetracyanamidogallate
2013-11-12

Abstract A tetracyanamidogallate with the formula LiSr 2 [Ga(CN 2 ) 4 ] was prepared from stoichiometric mixtures of SrF 2 , GaF 3 , and Li 2 (CN 2 ) in a fused silica tube. The formation of LiSr 2 [Ga(CN 2 ) 4 ] by solid‐state metathesis was studied by differential scanning calorimetry. A crystalline powder of LiSr 2 [Ga(CN 2 ) 4 ] was studied by X‐ray powder diffraction, and powder patterns were indexed isotypically to LiSr 2 [Al(CN 2 ) 4 ]. The crystal structure of LiSr 2 [Ga(CN 2 ) 4 ] was refined by single‐crystal X‐ray diffraction, thus indicating a disorder of Li + and Ga 3+ ions that was investigated by the means of 71 Ga solid‐state magic‐angle spinning (MAS) NMR spectroscopic measurements and DFT calculations.
Population shift of binding pocket size and dynamic correlation analysis shed new light on the anticooperative mechanism of PII protein
2013-11-12

Abstract P II protein is one of the largest families of signal transduction proteins in archaea, bacteria, and plants, controlling key processes of nitrogen assimilation. An intriguing characteristic for many P II proteins is that the three ligand binding sites exhibit anticooperative allosteric regulation. In this work, P II protein from Synechococcus elongatus , a model for cyanobacteria and plant P II proteins, is utilized to reveal the anticooperative mechanism upon binding of 2‐oxoglutarate (2‐OG). To this end, a method is proposed to define the binding pocket size by identifying residues that contribute greatly to the binding of 2‐OG. It is found that the anticooperativity is realized through population shift of the binding pocket size in an asymmetric manner. Furthermore, a new algorithm based on the dynamic correlation analysis is developed and utilized to discover residues that mediate the anticooperative process with high probability. It is surprising to find that the T‐loop, which is believed to be responsible for mediating the binding of P II with its target proteins, also takes part in the intersubunit signal transduction process. Experimental results of P II variants further confirmed the influence of T‐loop on the anticooperative regulation, especially on binding of the third 2‐OG. These discoveries extend our understanding of the P II T‐loop from being essential in versatile binding of target protein to signal‐mediating in the anticooperative allosteric regulation. Proteins 2014; 82:1048–1059. © 2013 The Authors. Proteins: Structure, Function, and Bioinformatics Published by Wiley Periodicals, Inc.
Dense isocontour imaging
2013-11-12

We present an imaging technique intended to explore multi-scale image structures, represented by isophotes (lines of constant brightness) for photo images or in general case isolines. The cornerstone of the discussed technique is a view dependent periodic transfer function with the period depending on the gradient magnitude of the underlying scalar function such as to create a dense visualization independent of the gradient magnitude. We demonstrate that our approach is easy to implement, computationally efficient, and suitable for the fields that have reasonably structured isolines, i.e., that are sufficiently smooth.
Associations between Physical and Cognitive Doping – A Cross-Sectional Study in 2.997 Triathletes
2013-11-13

The use of substances to improve physical and cognitive performance was associated on both levels of legality (enhancement vs. doping) suggesting that athletes do not use substances for a specific goal but may have a general propensity to enhance. This finding is important for understanding why people use such substances. Consequently, more effective prevention programs against substance abuse and doping could be developed.
Role of Somatosensory Cortex in Visuospatial Attention
2013-11-13

The human somatosensory cortex (S1) is not among the brain areas usually associated with visuospatial attention. However, such a function can be presumed, given the recently identified eye proprioceptive input to S1 and the established links between gaze and attention. Here we investigated a rare patient with a focal lesion of the right postcentral gyrus that interferes with the processing of eye proprioception without affecting the ability to locate visual objects relative to her body or to execute eye movements. As a behavioral measure of spatial attention, we recorded fixation time during visual search and reaction time for visual discrimination in lateral displays. In contrast to a group of age-matched controls, the patient showed a gradient in looking time and in visual sensitivity toward the midline. Because an attention bias in the opposite direction, toward the ipsilesional space, occurs in patients with spatial neglect, in a second study, we asked whether the incidental coinjury of S1 together with the neglect-typical perisylvian lesion leads to a milder neglect. A voxelwise lesion behavior mapping analysis of a group of right-hemisphere stroke patients supported this hypothesis. The effect of an isolated S1 lesion on visual exploration and visual sensitivity as well as the modulatory role of S1 in spatial neglect suggest a role of this area in visuospatial attention. We hypothesize that the proprioceptive gaze signal in S1, although playing only a minor role in locating visual objects relative to the body, affects the allocation of attention in the visual space.
2A and the Auxin-Based Degron System Facilitate Control of Protein Levels in Plasmodium falciparum
2013-11-13

Analysis of gene function in Plasmodium falciparum, the most important human malaria parasite, is restricted by the lack of robust and simple reverse genetic tools. Approaches to manipulate protein levels post-translationally are powerful tools to study protein-off effects especially in the haploid malaria parasite where genetic knockouts of essential genes are lethal. We investigated if the auxin-inducible degron system is functional in P. falciparum and found that degron-tagged yellow fluorescent protein levels were efficiently reduced upon addition of auxin which otherwise had no effect on parasite viability. The genetic components required in this conditional approach were co-expressed in P. falciparum by applying the small peptide 2A. 2A is a self-processing peptide from Foot-And-Mouth Disease virus that allows the whole conditional system to be accommodated on a single plasmid vector and ensures stoichiometric expression levels.
Cephalo-traumatic secretion transfer in a hermaphrodite sea slug
2013-11-13

Mating rituals in the animal kingdom are often quite extraordinary, in particular when mating is traumatic. We here describe the exceptional traumatic mating behaviour of the currently undescribed sea slug, Siphopteron sp. 1. Similar to four congeners, Siphopteron sp. 1 routinely exhibits traumatic secretion transfer through a stylet-like penis appendage. Contrary to previous descriptions, however, prostate secretions are injected centrally into the partner's forehead, representing, to our knowledge, the first-known instance of ‘cephalo-traumatic secretion transfer’. We further provide a comparative quantification of within- and between-species variation in injection sites and derive a potential neurophysiological function of prostate secretions that are injected close to, or into, the central nervous system.
Electrical Stimulation of the Human Homolog of the Medial Superior Temporal Area Induces Visual Motion Blindness
2013-11-13

Despite tremendous advances in neuroscience research, it is still unclear how neuronal representations of sensory information give rise to the contents of our perception. One of the first and also the most compelling pieces of evidence for direct involvement of cortical signals in perception comes from electrical stimulation experiments addressing the middle temporal (MT) area and the medial superior temporal (MST) area: two neighboring extrastriate cortical areas of the monkey brain housing direction-sensitive neurons. Here we have combined fMRI with electrical stimulation in a patient undergoing awake brain surgery, to separately probe the functional significance of the human homologs, i.e., area hMT and hMST, on motion perception. Both the stimulation of hMT and hMST made it impossible for the patient to perceive the global visual motion of moving random dot patterns. Although visual motion blindness was predominantly observed in the contralateral visual field, stimulation of hMST also affected the ipsilateral hemifield. These results suggest that early visual cortex up to the stage of MT is not sufficient for the perception of global visual motion. Rather, visual motion information must be mediated to higher-tier cortical areas, including hMST, to gain access to conscious perception.
Microbially enhanced dissolution of HgS in an acid mine drainage system in the California Coast Range
2013-11-13

Abstract Mercury sulfides (cinnabar and metacinnabar) are the main ores of H g and are relatively stable under oxic conditions (K sp = 10 −54 and 10 −52 , respectively). However, until now their stability in the presence of micro‐organisms inhabiting acid mine drainage ( AMD ) systems was unknown. We tested the effects of the AMD microbial community from the inoperative H g mine at N ew I dria, CA , present in sediments of an AMD settling pond adjacent to the main waste pile and in a microbial biofilm on the surface of this pond, on the solubility of crystalline HgS. A 16S r RNA gene clone library revealed that the AMD microbial community was dominated by F e‐oxidizing (orders F erritrophicales and G allionellas) and S ‐oxidizing bacteria ( Thiomonas sp .), with smaller amounts (≤6%) being comprised of the orders Xanthomondales and Rhodospirillales. Though the order Ferritrophicales dominate the 16S rRNA clones (&gt;60%), q PCR results of the microbial community indicate that the Thiomonas sp . represents ~55% of the total micro‐organisms in the top 1 cm of the AMD microbial community. Although supersaturated with respect to cinnabar and metacinnabar, microcosms inoculated with the AMD microbial community were capable of releasing significantly more Hg into solution compared to inactivated or abiotic controls. Four different Hg‐containing materials were tested for bacterially enhanced HgS dissolution: pure cinnabar, pure metacinnabar, mine tailings, and calcine material (processed ore). In the microcosm with metacinnabar, the presence of the AMD microbial community resulted in an increase of dissolved Hg concentrations up to 500 μg L ‐1 during the first 30 days of incubation. In abiotic control microcosms, dissolved Hg concentrations did not increase above 100 ng L −1 . When Hg concentrations were below 50 μg L ‐1 , the Fe‐oxidizing bacteria in the AMD microbial community were still capable of oxidizing Fe(II) to Fe(III) in the AMD solution, whereas concentrations above 50 μg L −1 resulted in inhibition of microbial iron oxidation. Our experiments show that the AMD microbial community contributes to the dissolution of mercury sulfide minerals. These findings have major implications for risk assessment and future management of inoperative Hg mines worldwide.
Fetal behavioral states are stable over daytime – evidence by longitudinal and cross-sectional fetal biomagnetic recordings
2013-11-13

Abstract Aims: Fetal behavioral states can be distinguished by biomagnetic recordings. We performed a longitudinal and a cross-sectional study to address the question whether the distribution of fetal behavioral states changes during the daytime. Methods: For the longitudinal study, 32 magnetocardiographic recordings were performed on a singleton pregnancy on a weekly basis. On each examination day, two recordings were performed at different times between 25 and 40 weeks of gestation. For the cross-sectional study, fetal magnetocardiograms (fMCG) were recorded in a group of 32 singleton pregnancies matched for gestational age and daytime to the longitudinal study. The recordings were separated into two gestational age groups (less and more than 32 weeks). Fetal behavioral states were extracted from actocardiograms generated from MCG. Results: No significant differences in fetal behavioral state distribution were found between morning and afternoon recordings in either the longitudinal or the cross-sectional study. Conclusion: This is the first magnetographic approach to show that daytime does not influence the distribution of fetal behavioral states in standardized recordings of 30 min length. This result implies that fetal magnetography recordings at normal daytimes can be combined without a bias and future recordings can be conducted independently of daytime as long as the varying behavioral states are generally taken into account during analysis.
Memory for Past Public Events Depends on Retrieval Frequency but not Memory Age in Alzheimer's Disease
2013-11-13

Alzheimer's disease (AD) is characterized by retrograde memory deficits primarily caused by dysfunction of the hippocampal complex. Unresolved questions exist concerning the time course of hippocampal involvement in conscious recollection of declarative knowledge, as reports of temporal gradients of retrograde amnesia have been inconclusive. The aim of this study was to examine whether the extent and severity of retrograde amnesia is mediated by retrieval frequency or, in contrast, whether it depends on the age of the memory according to the assumptions of the main current theories of memory formation. We compared recall of past public events in patients with AD and healthy control (HC) individuals using the Historic Events Test (HET). The HET assesses knowledge about famous public events of the past 60 years divided into four time segments and consists of subjective memory rating, dating accuracy, and contextual memory tasks. Although memory for public events was impaired in AD patients, there was a strong effect of retrieval frequency across all time segments and both groups. As AD and HC groups derived similar benefits from greater retrieval frequency, cortical structures other than the hippocampal complex may mediate memory retrieval. These findings suggest that more frequently retrieved events and facts become more independent of the hippocampal complex and thus better protected against early damage of AD. This could explain why cognitive activity may delay the onset of memory decline in persons who develop AD.
Cardiovascular magnetization transfer ratio imaging compared with histology: A postmortem study
2013-11-13

Cardiovascular magnetization transfer ratio (MTR) imaging by steady state free precession is a promising imaging method to assess microstructural changes within the myocardium. Hence, MTR imaging was correlated to histological analysis. Three postmortem cases were selected based on a suspicion of myocardial infarction. MTR and T 2 ‐weighted ( T 2w ) imaging was performed, followed by autopsy and histological analysis. All tissue abnormalities, identified by autopsy or histology, were retrospectively selected on visually matched MTR and T 2w images, and corresponding MTR values compared with normal appearing tissue. Regions of elevated MTR (up to approximately 20%, as compared to normal tissue), appearing hypo‐intense in T 2w ‐images, revealed the presence of fibrous tissue in microscopic histological analysis. Macroscopic observation (autopsy) described scar tissue only in one case. Regions of reduced MTR (up to approximately 20%) corresponded either to (i) the presence of edema, appearing hyperintense in T 2w ‐images and confirmed by autopsy, or to (ii) inflammatory granulocyte infiltration at a microscopic level, appearing as hypo‐intense T 2w ‐signal, but not observed by autopsy. Findings from cardiovascular MTR imaging corresponded to histology results. In contrast to T 2w ‐imaging, MTR imaging discriminated between normal myocardium, scar tissue and regions of acute myocardial infarction in all three cases. J. Magn. Reson. Imaging 2014;40:915–919 . © 2013 Wiley Periodicals, Inc.
Complete Mitochondrial Genomes of Ancient Canids Suggest a European Origin of Domestic Dogs
2013-11-14

Dog Domestication The precise details of the domestication and origins of domestic dogs are unclear. Thalmann et al. (p. 871 ; see the cover) analyzed complete mitochondrial genomes from present-day dogs and wolves, as well as 18 fossil canids dating from 1000 to 36,000 years ago from the Old and New Worlds. The data suggest that an ancient, now extinct, central European population of wolves was directly ancestral to domestic dogs. Furthermore, several ancient dogs may represent failed domestication events.