julilili42/papers huggingface dataset:
Fear of progression in patients with low-risk malignant melanoma.
2017-05-20

e21615 Fear of progression in patients with low-risk malignant melanoma Fear of cancer progression (FoP) is one of the problems most commonly reported by cancer patients and is among the most prevalent cancer-related worries in cancer survivors. FCR is highly variable in different cancer entities. Background: This study aimed to elicit the prevalence and significance of FCR in melanoma patients with low risk tumors and further to assess psychosocial and demographic factors predicting severity of FoP as well as to determine the impact of FoP on quality of life (QoL). Methods: In total, 133 patients with low-risk melanoma (pT1a) completed the short version of the Fear of Progression Questionnaire (FoP-Q-SF), the Hospital Anxiety and Depression Scale (HADS), and the EQ-5D questionnaire, as well as self-constructed questions on the socio-demographic background. Results: MeanFoP-Q-SF sum score was 30.1 points (± 8.4 points SD) and the median 29 points. Two thirds of patients deviated not more than 1 SD from the mean. Risk factors for elevated FoP were female gender (p &lt; 0.01), young age (p = 0.04) and working (p = 0.02) patients and patients with severe comorbidities (p = 0.03). Cancer in closely related persons predicted higher FoP (p &lt; 0.01). HADS anxiety scale (r = 0.49, p &lt; 0.01) and depression scale (r = 0.26, p &lt; 0.01) correlated with FoP. A negative correlation with the EQ-5D index was found (r = -0.34, p &lt; 0.01). Conclusions: As in many other malignancies,FoP is prevalent in low-risk melanoma patients and is associated with reduced QoL. Severe comorbidities, cancer in related persons, gender and income could be identified as predictors of FoP. Considerable high levels of FoP even in patients with low-risk malignancies underline the need of psychosocial support and intervention for special subgroups of melanoma patients to enable the patient to manage FoP more successfully.
TRPV4 plays a role in breast cancer cell migration via Ca2+-dependent activation of AKT and downregulation of E-cadherin cell cortex protein
2017-05-22

Abstract TRPV4 belongs to the ‘Transient Receptor Potential’ (TRP) superfamily. It has been identified to profoundly affect a variety of physiological processes, including nociception, heat sensation and inflammation. Unlike other TRP superfamily channels, its role in cancers are unknown until recently when we reported TRPV4 to be required for cancer cell softness that may promote breast cancer cell extravasation and metastasis. Here, we elucidated the molecular mechanisms mediated by TRPV4 in the metastatic breast cancer cells. TRPV4-mediated signaling was demonstrated to involve Ca 2+ -dependent activation of AKT and downregulation of E-cadherin expression, which was abolished upon TRPV4 silencing. Functionally, TRPV4-enhanced breast caner cell transendothelial migration requires AKT activity while a combination of transcriptional and post-translational regulation contributed to the TRPV4-mediated E-cadherin downregulation. Finally, mass spectrometry analysis revealed that TRPV4 is required for the expression of a network of secreted proteins involved in extracellular matrix remodeling. In conclusion, TRPV4 may regulate breast cancer metastasis by regulating cell softness through the Ca 2+ -dependent AKT-E-cadherin signaling axis and regulation of the expression of extracellular proteins.
Messinian age and savannah environment of the possible hominin Graecopithecus from Europe
2017-05-22

Dating fossil hominids and reconstructing their environments is critically important for understanding human evolution. Here we date the potentially oldest hominin, Graecopithecus freybergi from Europe and constrain the environmental conditions under which it thrived. For the Graecopithecus-bearing Pikermi Formation of Attica/Greece, a saline aeolian dust deposit of North African (Sahara) provenance, we obtain an age of 7.37-7.11 Ma, which is coeval with a dramatic cooling in the Mediterranean region at the Tortonian-Messinian transition. Palaeobotanic proxies demonstrate C4-grass dominated wooded grassland-to-woodland habitats of a savannah biome for the Pikermi Formation. Faunal turnover at the Tortonian-Messinian transition led to the spread of new mammalian taxa along with Graecopithecus into Europe. The type mandible of G. freybergi from Pyrgos (7.175 Ma) and the single tooth (7.24 Ma) from Azmaka (Bulgaria) represent the first hominids of Messinian age from continental Europe. Our results suggest that major splits in the hominid family occurred outside Africa.
Potential hominin affinities of Graecopithecus from the Late Miocene of Europe
2017-05-22

The split of our own clade from the Panini is undocumented in the fossil record. To fill this gap we investigated the dentognathic morphology of Graecopithecus freybergi from Pyrgos Vassilissis (Greece) and cf. Graecopithecus sp. from Azmaka (Bulgaria), using new μCT and 3D reconstructions of the two known specimens. Pyrgos Vassilissis and Azmaka are currently dated to the early Messinian at 7.175 Ma and 7.24 Ma. Mainly based on its external preservation and the previously vague dating, Graecopithecus is often referred to as nomen dubium. The examination of its previously unknown dental root and pulp canal morphology confirms the taxonomic distinction from the significantly older northern Greek hominine Ouranopithecus. Furthermore, it shows features that point to a possible phylogenetic affinity with hominins. G. freybergi uniquely shares p4 partial root fusion and a possible canine root reduction with this tribe and therefore, provides intriguing evidence of what could be the oldest known hominin.
A comparison of optimization algorithms for localized in vivo B0 shimming
2017-05-22

Purpose To compare several different optimization algorithms currently used for localized in vivo B 0 shimming, and to introduce a novel, fast, and robust constrained regularized algorithm ( ConsTru ) for this purpose. Methods Ten different optimization algorithms (including samples from both generic and dedicated least‐squares solvers, and a novel constrained regularized inversion method) were implemented and compared for shimming in five different shimming volumes on 66 in vivo data sets from both 7 T and 9.4 T. The best algorithm was chosen to perform single‐voxel spectroscopy at 9.4 T in the frontal cortex of the brain on 10 volunteers. Results The results of the performance tests proved that the shimming algorithm is prone to unstable solutions if it depends on the value of a starting point, and is not regularized to handle ill‐conditioned problems. The ConsTru algorithm proved to be the most robust, fast, and efficient algorithm among all of the chosen algorithms. It enabled acquisition of spectra of reproducible high quality in the frontal cortex at 9.4 T. Conclusions For localized in vivo B 0 shimming, the use of a dedicated linear least‐squares solver instead of a generic nonlinear one is highly recommended. Among all of the linear solvers, the constrained regularized method ( ConsTru ) was found to be both fast and most robust. Magn Reson Med 79:1145–1156, 2018. © 2017 International Society for Magnetic Resonance in Medicine.
Conscientiousness but not agreeableness mediates females’ tendency toward being a morning person
2017-05-22

Individuals differ in their chronotype, and some are identified as morning ones and others as evening ones. Earlier studies showed that women were higher on morningness, conscientiousness, and agreeableness. In this study, we aimed at exploring the mediational effects of conscientiousness and agreeableness in the relationship of gender and morningness‐eveningness. Participants were 669 university students. Results supported positive relationships between morningness and conscientiousness and agreeableness and between conscientiousness and agreeableness. Females were higher on all these three variables. Mediation analyses suggested that the effect of gender (here females) on chronotype (here morningness) was mediated by conscientiousness but not agreeableness so that after the mediation partially occurred, the gender's effect did not remain significant anymore. This study backed our hypothesis that conscientiousness might play a more pronounced role than the intrinsic diurnal rhythm concerning the sex differences in chronotype.
Mutations of MAP2K1 are frequent in pediatric-type follicular lymphoma and result in ERK pathway activation
2017-05-23

Key Points TNFRSF14 and MAP2K1 mutations are frequent in PTFL but do not occur together in the majority of cases. MAP2K1 mutations lead to activation of the downstream target phosphorylated extracellular signal-regulated kinase.
Genetic Mouse Models with Intestinal-Specific Tight Junction Deletion Resemble an Ulcerative Colitis Phenotype
2017-05-23

Genetic mouse models with intestinal deletion of kindlin 1 and 2 resulted in TJ deletion and revealed pathophysiological features of impaired PC secretion to the mucus leading to mucosal inflammation compatible with human UC.
Lesion characteristics driving right-hemispheric language reorganization in congenital left-hemispheric brain damage
2017-05-23

Pre- or perinatally acquired ("congenital") left-hemispheric brain lesions can be compensated for by reorganizing language into homotopic brain regions in the right hemisphere. Language comprehension may be hemispherically dissociated from language production. We investigated the lesion characteristics driving inter-hemispheric reorganization of language comprehension and language production in 19 patients (7-32years; eight females) with congenital left-hemispheric brain lesions (periventricular lesions [n=11] and middle cerebral artery infarctions [n=8]) by fMRI. 16/17 patients demonstrated reorganized language production, while 7/19 patients had reorganized language comprehension. Lesions to the insular cortex and the temporo-parietal junction (predominantly supramarginal gyrus) were significantly more common in patients in whom both, language production and comprehension were reorganized. These areas belong to the dorsal stream of the language network, participating in the auditory-motor integration of language. Our data suggest that the integrity of this stream might be crucial for a normal left-lateralized language development.
Molecular markers of anti-malarial drug resistance in Central, West and East African children with severe malaria
2017-05-23

Artemisinins are still highly efficacious in large malaria-endemic regions though declining efficacy has occurred in Southeast Asia. The return of chloroquine-sensitive strains following the removal of drug pressure is observed. However, selection of wild-type alleles in the multidrug-resistance gene and the increased gene copy number is associated with reduced lumefantrine sensitivity. This study indicates a need to constantly monitor drug resistance to artemisinin in field isolates from malaria-endemic countries.
Rediscovery of the water mite Atractides circumcinctus Schwoerbel, 1956 (Acari: Hydrachnidia) in the Black Forest National Park
2017-05-23

Two populations of the water mite Atractides circumcinctus Schwoerbel, 1956 are recorded from the Black Forest National Park (Germany, Baden-Württemberg). This species had not been found since its first description and some additional records published by Schwoerbel (1958). A redescription is given, the morphological variability and diagnostic features of the species are discussed.
Suicidal death of erythrocytes in cancer and its chemotherapy: A potential target in the treatment of tumor‐associated anemia
2017-05-24

In analogy to apoptosis of nucleated cells, erythrocytes may enter eryptosis characterized by cell shrinkage and cell membrane scrambling. Eryptotic erythrocytes are rapidly cleared from circulating blood and may adhere to the vascular wall. Stimulation of eryptosis thus impairs microcirculation and leads to anemia as soon as the loss of erythrocytes cannot be fully compensated by enhanced erythropoiesis. Signaling stimulating eryptosis includes increase of cytosolic Ca 2+ ‐activity, ceramide, caspases, calpain, p38‐kinase, protein‐kinase C, Janus‐activated kinase 3, casein‐kinase 1α, and cyclin‐dependent kinase 4. Eryptosis is inhibited by AMP‐activated kinase, p21‐activated kinase 2, cGMP‐dependent protein‐kinase, mitogen‐ and stress‐activated kinase, and sorafenib‐ and sunitinib‐sensitive tyrosine‐kinases. Eryptosis is triggered by complement, hyperosmotic shock, energy‐depletion, oxidative stress, multiple xenobiotics including diverse cytostatic drugs, diabetes, hepatic failure, iron‐deficiency, chronic kidney disease, hemolytic‐uremic‐syndrome, fever, systemic lupus erythematosus, infections, sepsis, sickle cell anemia, thalassemia, glucose‐6‐phosphate‐dehydrogenase deficiency, and Wilson ́s disease. Compelling evidence points to a decisive role of eryptosis in anemia of malignancy. As shown for lung cancer, eryptosis inducing plasma components accumulate in cancer patients and trigger oxidative stress and ceramide. The tumor‐induced eryptosis leads to anemia despite increased erythropoiesis. The stimulation of eryptosis in malignancy is compounded by cytostatic treatment, as a large number of cytostatic agents trigger eryptosis. Inhibiting eryptosis may be a useful strategy in reducing tumor‐induced anemia and impaired microcirculation. Inhibitors of eryptosis may, however, be harmful, if they similarly interfere with death of tumor cells. Clearly, additional experimental effort is required to achieve killing of tumor cells with simultaneous avoidance of stimulated eryptosis.
Occupational manual activity is reflected on the patterns among hand entheses
2017-05-24

Abstract Objectives In anthropological sciences, entheses are widely utilized as occupational stress markers. However, the reaction of entheseal surfaces to mechanical loading is not well understood. Furthermore, previous studies on entheses relied on the individuals' occupation‐at‐death. Past research by one of us has identified two patterns among hand entheses, proposing that they reflect two synergistic muscle groups. Here, we investigate the association between these patterns and habitual manual activity using an extensively documented skeletal sample and a three‐dimensional system of quantification. Materials and Methods The hand bones utilized belong to 45 individuals from mid‐19th century Basel. These were male adults (18 to 48 years old) who were not directly related, showed no manual pathological conditions, and whose occupational activities during their lifetime were clearly documented and could be evaluated according to historical sources. The patterns of entheses were explored using principal component analysis on both raw and size‐adjusted variables. The influence of age‐at‐death, body mass, and bone length was assessed through correlation tests. Results The analysis showed that the previously proposed patterns of entheses are present in our sample. Individuals with the same or comparable occupations presented similar entheseal patterns. These results were not considerably affected by entheseal overall size, age‐at‐death, body mass, or bone length. Discussion Individuals involved in intense manual labor during their lifetime presented a distinctive pattern of hand entheses, consistent with the application of high grip force. By contrast, individuals with less strenuous and/or highly mechanized occupations showed an entheseal pattern related to the thumb intrinsic muscles.
Ability to Gain Control Over One’s Own Brain Activity and its Relation to Spiritual Practice: A Multimodal Imaging Study
2017-05-24

Spiritual practice, such as prayer or meditation, is associated with focusing attention on internal states and self-awareness processes. As these cognitive control mechanisms presumably are also important for neurofeedback (NF), we investigated whether people who pray frequently (<i>N</i> = 20) show a higher ability of self-control over their own brain activity compared to a control group of individuals who rarely pray (<i>N</i> = 20). All participants underwent structural magnetic resonance imaging (MRI) and one session of sensorimotor rhythm (SMR, 12-15 Hz) based NF training. Individuals who reported a high frequency of prayer showed improved NF performance compared to individuals who reported a low frequency of prayer. The individual ability to control one's own brain activity was related to volumetric aspects of the brain. In the low frequency of prayer group, gray matter volumes in the right insula and inferior frontal gyrus were positively associated with NF performance, supporting prior findings that more general self-control networks are involved in successful NF learning. In contrast, participants who prayed regularly showed a negative association between gray matter volume in the left medial orbitofrontal cortex (Brodmann's area (BA) 10) and NF performance. Due to their regular spiritual practice, they might have been more skillful in gating incoming information provided by the NF system and avoiding task-irrelevant thoughts.
Gait Is Associated with Cognitive Flexibility: A Dual-Tasking Study in Healthy Older People
2017-05-24

<b>Objectives:</b> To analyze which gait parameters are primarily influenced by cognitive flexibility, and whether such an effect depends on the walking condition used. <b>Design:</b> Cross-sectional analysis. <b>Setting:</b> Tübingen evaluation of Risk factors for Early detection of Neurodegenerative Disorders. <b>Participants:</b> A total of 661 non-demented individuals (49-80 years). <b>Measurements:</b> A gait assessment with four conditions was performed: a 20 m walk at convenient speed (C), at fast speed (F), at fast speed while checking boxes (FB), and while subtracting serial 7s (FS). Seven gait parameters from a wearable sensor-unit (McRoberts, Netherlands) were compared with delta Trail-Making-Test (dTMT) values, which is a measure of cognitive flexibility. Walking strategies of good and poor dTMT performers were compared by evaluating the patterns of gait parameters across conditions. <b>Results:</b> Five parameters correlated significantly with the dTMT in the FS condition, two parameters in the F and FB condition, and none in the C condition. Overall correlations were relatively weak. Gait speed was the gait parameter that most strongly correlated with the dTMT (<i>r</i><sup>2</sup> = 7.4%). In good, but not poor, dTMT performers differences between FB and FS were significantly different in variability-associated gait parameters. <b>Conclusion:</b> Older individuals need cognitive flexibility to perform difficult walking conditions. This association is best seen in gait speed. New and particularly relevant for recognition and training of deficits is that older individuals with poor cognitive flexibility have obviously fewer resources to adapt to challenging walking conditions. Our findings partially explain gait deficits in older adults with poor cognitive flexibility.
AAV-Mediated Gene Supplementation Therapy in Achromatopsia Type 2: Preclinical Data on Therapeutic Time Window and Long-Term Effects
2017-05-24

Achromatopsia type 2 (ACHM2) is a severe, inherited eye disease caused by mutations in the <i>CNGA3</i> gene encoding the α subunit of the cone photoreceptor cyclic nucleotide-gated (CNG) channel. Patients suffer from strongly impaired daylight vision, photophobia, nystagmus, and lack of color discrimination. We have previously shown in the <i>Cnga</i>3 knockout (KO) mouse model of ACHM2 that gene supplementation therapy is effective in rescuing cone function and morphology and delaying cone degeneration. In our preclinical approach, we use recombinant adeno-associated virus (AAV) vector-mediated gene transfer to express the murine <i>Cnga3</i> gene under control of the mouse blue opsin promoter. Here, we provide novel data on the efficiency and permanence of such gene supplementation therapy in <i>Cnga3</i> KO mice. Specifically, we compare the influence of two different AAV vector capsids, AAV2/5 (Y719F) and AAV2/8 (Y733F), on restoration of cone function, and assess the effect of age at time of treatment on the long-term outcome. The evaluation included <i>in vivo</i> analysis of retinal function using electroretinography (ERG) and immunohistochemical analysis of vector-driven <i>Cnga3</i> transgene expression. We found that both vector capsid serotypes led to a comparable rescue of cone function over the observation period between 4 weeks and 3 months post treatment. In addition, a clear therapeutic effect was present in mice treated at 2 weeks of age as well as in mice treated at 3 months of age at the first assessment at 4 weeks after treatment. Importantly, the effect extended in both cases over the entire observation period of 12 months post treatment. However, the average ERG amplitude levels differed between the two groups, suggesting a role of the absolute age, or possibly, the associated state of the degeneration, on the achievable outcome. In summary, we found that the therapeutic time window of opportunity for AAV-mediated <i>Cnga3</i> gene supplementation therapy in the <i>Cnga3</i> KO mouse model extends at least to an age of 3 months, but is presumably limited by the condition, number and topographical distribution of remaining cones at the time of treatment. No impact of the choice of capsid on the therapeutic success was detected.
Reactivation of interference during sleep does not impair ongoing memory consolidation
2017-05-24

Memory consolidation during sleep is assumed to rely on the repeated reactivation of newly encoded memories particularly during slow wave sleep (SWS). It has been proposed that reactivated memories during sleep - like during wakefulness - undergo a labilisation process, enabling the strengthening and integration of new memories into pre-existing networks. Here, we tested this idea by introducing interference directly during sleep in the reactivation/consolidation phase. We predicted that cueing interfering memories during sleep would impair the consolidation of recently learned memories. Participants learned a visuo-spatial memory task before they were allowed to sleep for 40 min. During sleep, and particularly during SWS, subjects were presented with interference via odour cueing (compared to a no interference vehicle condition). In contrast to our hypothesis, cueing of the interference during sleep did not impair consolidation of the newly learned memories: odour and vehicle conditions did not differ in memory recall after sleep. On the contrary, subjects even displayed significantly fewer intrusions from the interference during memory recall when the odour was presented during sleep. These findings suggest that interference presentation during sleep does not disrupt endogenous memory consolidation, but might even facilitate pattern separation and memory stabilisation through generalisation processes.