julilili42/papers huggingface dataset:
U-Pb zircon and K-Ar geochronology reveal the emplacement and cooling history of the Late Cretaceous Beypazarı granitoid, central Anatolia, Turkey
2014-06-24

The Beypazarı granitoid has been studied with respect to multi-radiometric dating and oxygen isotopic geothermometry. Radiometric dating of the granitoid yields zircon U-Pb isochron ages ranging from 72.5 ± 12.6 to 78.6 ± 4.7, and K-Ar ages of 71.4 ± 2.8 to 74.9 ± 2.9 and 59.5 ± 2.2 to 75.4 ± 2.9 Ma for hornblende and biotite, respectively. Oxygen isotope thermometry for the granitoid gives temperatures of 550 ± 25°C to 605 ± 30, 390 ± 15 to 540 ± 25°C, and 481 ± 5 to 675 ± 10°C, for hornblende, biotite, and K-feldspar, respectively, when paired with quartz. The systematic differences among ages according to different techniques used on different minerals are used to reconstruct the cooling history of the granite. The results yield rapid cooling rates of 33.3°C/Ma from 800°C to 550°C, and slow cooling rates of about 15 ± 0.5°C/Ma from 550 to 300°C. Rapid subsolidus cooling between 600°C and 550°C is documented by 40Ar/39Ar ages on amphibole and biotite between 71.4 ± 2.8 and 75.4 ± 2.9 Ma. Younger ages on biotites from two samples (59.5 ± 2.2 and 64.4 ± 2.5) are probably caused by loss of Ar. The reason for this possible Ar loss can be interpreted as slower subsolidus cooling (~375°C) ages. There is an apparent spatial and temporal relationship between the intrusion-cooling of the Beypazarı granitoid and the evolution of the İzmir–Ankara–Erzincan ocean belonging to the northern Neo-Tethyan ocean domain.
Trastuzumab Administration in Patients with Metastatic Breast Cancer – Experience of a Large University Breast Center
2014-06-24

<b>Background:</b> Administered either alone or in combination with various cytostatic, endocrine or targeted therapies, trastuzumab significantly improves the prognosis of patients with HER2-positive breast cancer. As trastuzumab is effective across multiple lines of therapy in the metastatic setting (treatment beyond progression: TBP), it is often administered over a long period of time. The aim of this study was to evaluate the tolerability and clinical practice of long-term trastuzumab administration (> 1 year) in metastatic breast cancer patients treated in a large university breast center. <b>Methods:</b> Metastatic breast cancer patients who received at least 18 cycles of trastuzumab administered every three weeks at the University Gynecological Hospital of Tuebingen between 1999 and 2012 were included in this retrospective study. Typical combination drugs, side effects, and the impact of administration on left ventricular ejection fraction (LVEF) were investigated. <b>Results:</b> 72 patients were eligible for inclusion in the study. The mean number of administrations was 50.14 (SD: 27.51). In 53 patients the principle of TBP was followed across an average of 2.4 therapy lines. Classic cardiac risk factors were present at the beginning of trastuzumab treatment in 34 patients (47 %). Seven patients (10 %) experienced a decrease in LVEF during treatment, 9 patients (13 %) had hypersensitivity reactions. Treatment was discontinued in two patients due to side effects (1 × progressive LVEF decrease, 1 × intolerance). <b>Summary:</b> The administration of trastuzumab across multiple lines of therapy was generally tolerated well. Cardiac risk factors were not a limiting factor. If regular cardiac monitoring is done, trastuzumab appears not only to improve survival but also helps preserve the quality of life of patients with HER2-positive metastatic breast cancer.
Return of chloroquine-sensitive Plasmodium falciparum parasites and emergence of chloroquine-resistant Plasmodium vivax in Ethiopia
2014-06-25

The study reports for the first time the return of chloroquine sensitive P. falciparum in Ethiopia. These findings support the rationale for the use of CQ-based combination drugs as a possible future alternative.
Pure and syndromic optic atrophy explained by deep intronic OPA1 mutations and an intralocus modifier
2014-06-25

The genetic diagnosis in inherited optic neuropathies often remains challenging, and the emergence of complex neurological phenotypes that involve optic neuropathy is puzzling. Here we unravel two novel principles of genetic mechanisms in optic neuropathies: deep intronic OPA1 mutations, which explain the disease in several so far unsolved cases; and an intralocus OPA1 modifier, which explains the emergence of syndromic 'optic atrophy plus' phenotypes in several families. First, we unravelled a deep intronic mutation 364 base pairs 3' of exon 4b in OPA1 by in-depth investigation of a family with severe optic atrophy plus syndrome in which conventional OPA1 diagnostics including gene dosage analyses were normal. The mutation creates a new splice acceptor site resulting in aberrant OPA1 transcripts with retained intronic sequence and subsequent translational frameshift as shown by complementary DNA analysis. In patient fibroblasts we demonstrate nonsense mediated messenger RNA decay, reduced levels of OPA1 protein, and impairment of mitochondrial dynamics. Subsequent site-specific screening of >360 subjects with unexplained inherited optic neuropathy revealed three additional families carrying this deep intronic mutation and a base exchange four nucleotides upstream, respectively, thus confirming the clinical significance of this mutational mechanism. Second, in all severely affected patients of the index family, the deep intronic mutation occurred in compound heterozygous state with an exonic OPA1 missense variant (p.I382M; NM_015560.2). The variant alone did not cause a phenotype, even in homozygous state indicating that this long debated OPA1 variant is not pathogenic per se, but acts as a phenotypic modifier if it encounters in trans with an OPA1 mutation. Subsequent screening of whole exomes from >600 index patients identified a second family with severe optic atrophy plus syndrome due to compound heterozygous p.I382M, thus confirming this mechanism. In summary, we provide genetic and functional evidence that deep intronic mutations in OPA1 can cause optic atrophy and explain disease in a substantial share of families with unsolved inherited optic neuropathies. Moreover, we show that an OPA1 modifier variant explains the emergence of optic atrophy plus phenotypes if combined in trans with another OPA1 mutation. Both mutational mechanisms identified in this study-deep intronic mutations and intragenic modifiers-might represent more generalizable mechanisms that could be found also in a wide range of other neurodegenerative and optic neuropathy diseases.
Unemotional traits predict early processing deficit for fearful expressions in young violent offenders: an investigation using continuous flash suppression
2014-06-25

Background Research evidence suggests that cognitive and neural mechanisms involved in social information processing may underlie the key aspects associated with the emergence of aggression and psychopathy. Despite extensive research in this field, it is unclear whether this deficit relates to general attentional problems or affects early stages of information processing. Therefore, the aim was to explore the link between aggression, psychopathic traits, and the early processing deficits in young antisocial violent offenders (YAVOs) and healthy controls (CTLs). Method Participants were presented with rapidly changing Mondrian-like images in one eye, while a neutral or emotional (happy, angry, fearful, disgusted, surprised, sad) face was slowly introduced to the other eye. Participants indicated the location in which the face had appeared on the screen, reflecting the time when they became aware of the stimulus. The relative processing advantage was obtained by subtracting mean reaction times for emotional from neutral faces. Results The results indicated that individuals with higher levels of unemotional traits tended to exhibit an extensive early processing disadvantage for fearful facial expressions; this relationship was only evident in the YAVO as opposed to the CTL sample. Conclusions These findings indicate that an emotion processing deficit in antisocial individuals is present even at the most basic levels of processing and closely related to certain psychopathic traits. Furthermore, this early processing deficit appears to be highly specific to fearful expressions, which is consistent with predictions made by influential models of psychopathy. The clinical significance and potential implications of the results are discussed.
Modulation of the age at onset in spinocerebellar ataxia by CAG tracts in various genes
2014-06-26

Polyglutamine-coding (CAG)n repeat expansions in seven different genes cause spinocerebellar ataxias. Although the size of the expansion is negatively correlated with age at onset, it accounts for only 50-70% of its variability. To find other factors involved in this variability, we performed a regression analysis in 1255 affected individuals with identified expansions (spinocerebellar ataxia types 1, 2, 3, 6 and 7), recruited through the European Consortium on Spinocerebellar Ataxias, to determine whether age at onset is influenced by the size of the normal allele in eight causal (CAG)n-containing genes (ATXN1-3, 6-7, 17, ATN1 and HTT). We confirmed the negative effect of the expanded allele and detected threshold effects reflected by a quadratic association between age at onset and CAG size in spinocerebellar ataxia types 1, 3 and 6. We also evidenced an interaction between the expanded and normal alleles in trans in individuals with spinocerebellar ataxia types 1, 6 and 7. Except for individuals with spinocerebellar ataxia type 1, age at onset was also influenced by other (CAG)n-containing genes: ATXN7 in spinocerebellar ataxia type 2; ATXN2, ATN1 and HTT in spinocerebellar ataxia type 3; ATXN1 and ATXN3 in spinocerebellar ataxia type 6; and ATXN3 and TBP in spinocerebellar ataxia type 7. This suggests that there are biological relationships among these genes. The results were partially replicated in four independent populations representing 460 Caucasians and 216 Asian samples; the differences are possibly explained by ethnic or geographical differences. As the variability in age at onset is not completely explained by the effects of the causative and modifier sister genes, other genetic or environmental factors must also play a role in these diseases.
Brain-Computer Interfaces for Assessment and Communication in Disorders of Consciousness
2014-06-26

Many patients with Disorders of Consciousness (DOC) are misdiagnosed for a variety of reasons. These patients typically cannot communicate. Because such patients are not provided with the needed tools, one of their basic human needs remains unsatisfied, leaving them truly locked in to their bodies. This chapter first reviews current methods and problems of diagnoses and assistive technology for communication, supporting the view that advances in both respects are needed for patients with DOC. The authors also discuss possible solutions to these problems and introduce emerging developments based on EEG (Electroencephalography), fMRI (Functional Magnetic Resonance Imaging), and fNIRS (Functional Near-Infrared Spectroscopy) that have been validated with patients and healthy volunteers.
Combination of lidocaine suppository and periprostatic nerve block during transrectal prostate biopsy: A prospective randomized trial
2014-06-26

Objective To assess the most effective local analgesia during transrectal ultrasound‐guided prostate biopsy. Methods A total of 123 consecutive patients undergoing transrectal ultrasound‐guided prostate biopsy for elevated prostate‐specific antigen levels and/or a suspicious digital rectal examination were randomized to three groups. Patients received a 60‐mg lidocaine suppository (group 1, n = 41), a periprostatic nerve block (10‐mL injection of lidocaine hydrochloride; group 2, n = 41) or a combination of both (group 3, n = 41) before a 10‐core transrectal ultrasound‐guided biopsy. A total of 80.5% ( n = 99) of the patients underwent their first biopsy, 27.1% ( n = 22) their second and 2.4% ( n = 2) the third. Pain was evaluated on a 10‐point visual analog scale for each step of the procedure. Results Prostate‐specific antigen values ranged from 0.39 to 90.1 (mean [ SD ] 8.76 ng/mL [11.08 ng/mL]). Comparison of the median visual analog scale scores between groups 1 and 2 showed a significant difference ( P = 0.004). The differences in the outcomes between groups 1 and 3 ( P = 0.001), and groups 2 and 3 ( P = 0.001) were also significant. Patients of group 3 had the best output corresponding to the pain sensations and therefore the lowest visual analog scale scores. Conclusion The combination of lidocaine suppository and periprostatic lidocaine infiltration is more effective for pain control than either lidocaine suppository or periprostatic lidocaine infiltration alone in patients undergoing transrectal ultrasound‐guided prostate biopsy.
A new hand assessment instrument for severely affected stroke patients
2014-06-26

Background: Standard assessment instruments cannot differentiate patients with minimal residual hand function after stroke. As a result, changes in motor recovery are difficult to document using currently-available tests. In a controlled study with chronic stroke patients without residual finger extension, a new hand function test has been developed. This instrument, called Broetz Hand Test (BzH), allows to assess small variations in hand function in severely paralyzed stoke patients. The instrument is easy to use, and was developed using principles of motor learning and behavioral assessment. Methods: The instrument consists of seven daily life-oriented tasks, each of which asks for movement of the paralyzed hand. BzH of 20 patients after stroke was evaluated before and after a behavioral physiotherapy treatment. Sensitivity, inter-observer reliability, test-retest reliability and construct validity was calculated. Results: Two-tailed paired-samples t-test before and after treatment demonstrated sufficient sensitivity. Mean agreement between the raters resulted in an excellent interrater-reliability. Test-retest reliability between the pre- and post-treatment scores was 0.9. The correlation between BzH and standard test scores was statistically significant and demonstrated sufficient validity. Conclusion: The BzH is a valid and reliable tool to assess changes in hand function in severely paralyzed patients after stroke.
Bacterial Type III Secretion Systems: Specialized Nanomachines for Protein Delivery into Target Cells
2014-06-27

One of the most exciting developments in the field of bacterial pathogenesis in recent years is the discovery that many pathogens utilize complex nanomachines to deliver bacterially encoded effector proteins into target eukaryotic cells. These effector proteins modulate a variety of cellular functions for the pathogen's benefit. One of these protein-delivery machines is the type III secretion system (T3SS). T3SSs are widespread in nature and are encoded not only by bacteria pathogenic to vertebrates or plants but also by bacteria that are symbiotic to plants or insects. A central component of T3SSs is the needle complex, a supramolecular structure that mediates the passage of the secreted proteins across the bacterial envelope. Working in conjunction with several cytoplasmic components, the needle complex engages specific substrates in sequential order, moves them across the bacterial envelope, and ultimately delivers them into eukaryotic cells. The central role of T3SSs in pathogenesis makes them great targets for novel antimicrobial strategies.
Dendritic Cells and Anergic Type I NKT Cells Play a Crucial Role in Sulfatide-Mediated Immune Regulation in Experimental Autoimmune Encephalomyelitis
2014-06-28

Abstract CD1d-restricted NKT cells can be divided into two groups: type I NKT cells use a semi-invariant TCR, whereas type II express a relatively diverse set of TCRs. A major subset of type II NKT cells recognizes myelin-derived sulfatides and is selectively enriched in the CNS tissue during experimental autoimmune encephalomyelitis (EAE). We have shown that activation of sulfatide-reactive type II NKT cells by sulfatide prevents induction of EAE. In this article, we have addressed the mechanism of regulation, as well as whether a single immunodominant form of synthetic sulfatide can treat ongoing chronic and relapsing EAE in SJL/J mice. We have shown that the activation of sulfatide-reactive type II NKT cells leads to a significant reduction in the frequency and effector function of myelin proteolipid proteins 139–151/I-As–tetramer+ cells in lymphoid and CNS tissues. In addition, type I NKT cells and dendritic cells (DCs) in the periphery, as well as CNS-resident microglia, are inactivated after sulfatide administration, and mice deficient in type I NKT cells are not protected from disease. Moreover, tolerized DCs from sulfatide-treated animals can adoptively transfer protection into naive mice. Treatment of SJL/J mice with a synthetic cis-tetracosenoyl sulfatide, but not α-galactosylceramide, reverses ongoing chronic and relapsing EAE. Our data highlight a novel immune-regulatory pathway involving NKT subset interactions leading to inactivation of type I NKT cells, DCs, and microglial cells in suppression of autoimmunity. Because CD1 molecules are nonpolymorphic, the sulfatide-mediated immune-regulatory pathway can be targeted for development of non-HLA–dependent therapeutic approaches to T cell–mediated autoimmune diseases.
A Coding IRAK2 Protein Variant Compromises Toll-like receptor (TLR) Signaling and Is Associated with Colorectal Cancer Survival
2014-06-28

Within innate immune signaling pathways, interleukin-1 receptor-associated kinases (IRAKs) fulfill key roles downstream of multiple Toll-like receptors and the interleukin-1 receptor. Although human IRAK4 deficiency was shown to lead to severe immunodeficiency in response to pyogenic bacterial infection during childhood, little is known about the role of human IRAK2. We here identified a non-synonymous IRAK2 variant, rs35060588 (coding R214G), as hypofunctional in terms of NF-κB signaling and Toll-like receptor-mediated cytokine induction. This was due to reduced ubiquitination of TRAF6, a key step in signal transduction. IRAK2 rs35060588 occurs in 3-9% of individuals in different ethnic groups, and our studies suggested a genetic association of rs35060588 with colorectal cancer survival. This for the first time implicates human IRAK2 in a human disease and highlights the R214G IRAK2 variant as a potential novel and broadly applicable biomarker for disease or as a therapeutic intervention point.
Switching Intravitreal anti-VEGF Treatment in Neovascular Age-Related Macular Degeneration
2014-06-28

Purpose To compare the outcomes after switching between bevacizumab and ranibizumab therapy due to poor treatment effect in neovascular age-related macular degeneration (AMD). Methods This is a retrospective review of patients with neovascular AMD with first treatment using intravitreal bevacizumab (group 1) or ranibizumab (group 2) who switched to the other drug due to poor treatment effect. Primary outcome measures were change in mean best-corrected visual acuity (BCVA) and mean central retinal thickness (CRT) at 1 year and last visit. Results Eighty-seven eyes met the inclusion criteria. In group 1 (43 eyes), the mean BCVA decreased from 20/94 to 20/100 at 1 year after being switched (p = 0.573) and to 20/150 (p = 0.015) at final visit (mean 29.2 months, range 12-53). In group 2 (44 eyes), mean BCVA decreased from 20/72 to 20/90 (p = 0.401) and 20/100 (p = 0.081) at 1 year after switch and at final visit (mean 20.1 months, range 10-40), respectively. The mean CRT at switch, 1 year after switch, and at final visit were 344.4 ± 140 μm (mean ± SD), 286.26 ± 155 μm (p = 0.019), and 290.58 ± 196 μm (p = 0.009) in group 1 and 329.36 ± 144 μm, 302.0 ± 179 μm (p = 0.215), and 309.5 ± 220 μm (p = 0.154) in group 2, respectively. Conclusions The mean BCVA decreased over time in both groups; however, nearly 30% of the eyes in each group showed vision improvement after switching. Mean CRT decreased in both groups, which was more pronounced after being switched from bevacizumab to ranibizumab. In neovascular AMD, a switch between ranibizumab and bevacizumab can be considered as a further therapy option if poor treatment effect is seen with the initial therapy.
Emotion categorization of body expressions in narrative scenarios
2014-06-30

Humans can recognize emotions expressed through body motion with high accuracy even when the stimuli are impoverished. However, most of the research on body motion has relied on exaggerated displays of emotions. In this paper we present two experiments where we investigated whether emotional body expressions could be recognized when they were recorded during natural narration. Our actors were free to use their entire body, face, and voice to express emotions, but our resulting visual stimuli used only the upper body motion trajectories in the form of animated stick figures. Observers were asked to perform an emotion recognition task on short motion sequences using a large and balanced set of emotions (amusement, joy, pride, relief, surprise, anger, disgust, fear, sadness, shame, and neutral). Even with only upper body motion available, our results show recognition accuracy significantly above chance level and high consistency rates among observers. In our first experiment, that used more classic emotion induction setup, all emotions were well recognized. In the second study that employed narrations, four basic emotion categories (joy, anger, fear, and sadness), three non-basic emotion categories (amusement, pride, and shame) and the "neutral" category were recognized above chance. Interestingly, especially in the second experiment, observers showed a bias toward anger when recognizing the motion sequences for emotions. We discovered that similarities between motion sequences across the emotions along such properties as mean motion speed, number of peaks in the motion trajectory and mean motion span can explain a large percent of the variation in observers' responses. Overall, our results show that upper body motion is informative for emotion recognition in narrative scenarios.
Proposal: Different types of alteration and loss of consciousness in epilepsy
2014-06-30

Summary There are at least five types of alterations of consciousness that occur during epileptic seizures: auras with illusions or hallucinations, dyscognitive seizures, epileptic delirium, dialeptic seizures, and epileptic coma. Each of these types of alterations of consciousness has a specific semiology and a distinct pathophysiologic mechanism. In this proposal we emphasize the need to clearly define each of these alterations/loss of consciousness and to apply this terminology in semiologic descriptions and classifications of epileptic seizures. The proposal is a consensus opinion of experienced epileptologists, and it is hoped that it will lead to systematic studies that will allow a scientific characterization of the different types of alterations/loss of consciousness described in this article.