We present new constraints on the dark matter-induced annual modulation signal using 1.7 years of COSINE-100 data with a total exposure of 97.7 kg yr. The COSINE-100 experiment, consisting of 106 kg ...of NaI(Tl) target material, is designed to carry out a model-independent test of DAMA/LIBRA's claim of WIMP discovery by searching for the same annual modulation signal using the same NaI(Tl) target. The crystal data show a 2.7 cpd/kg/keV background rate on average in the 2-6 keV energy region of interest. Using a χ-squared minimization method we observe best fit values for modulation amplitude and phase of 0.0092±0.0067 cpd/kg/keV and 127.2±45.9 d, respectively.
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CMK, CTK, FMFMET, IJS, NUK, PNG, UM
Abstract Objectives The aim of this prospective multicenter study was to evaluate and compare the diagnostic performance of PET/CT, MRI and transvaginal two-dimensional ultrasound (2DUS) in the ...preoperative assessment of endometrial cancer (EC). Methods 318 consecutive women with EC were included when referred to three Danish tertiary gynecological centers for surgical treatment. Preoperatively they were PET/CT-, MRI-, and 2DUS scanned. The imaging results were compared to the final pathological findings. This study was approved by the National Committee on Health Research Ethics. Results For predicting myometrial invasion, we found sensitivity, specificity, PPV, NPV, and accuracy for PET/CT to be 93%, 49%, 41%, 95% and 61%, for MRI to be 87%, 57%, 44%, 92%, and 66% and for 2DUS to be 71%, 72%, 51%, 86% and 72%. For predicting cervical invasion, the values were 43%, 94%, 69%, 85% and 83%, respectively, for PET/CT, 33%, 95%, 60%, 85%, and 82%, respectively, for MRI, and 29%, 92%, 48%, 82% and 78% for 2DUS. Finally, for lymph node metastases, the values were 74%, 93%, 59%, 96%, and 91% for PET/CT and 59%, 93%, 40%, 97% and 90% for MRI. When comparing the diagnostic performance we found PET/CT, MRI and 2DUS to be comparable in predicting myometrial invasion. For cervical invasion and lymph node metastases, however, PET/CT was the best. Conclusions None of the modalities can yet replace surgical staging. However, they all contributed to important knowledge and were, furthermore, able to upstage low-risk patients who would not have been recommended lymph node resection based on histology and grade alone.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UL, UM, UPCLJ, UPUK
Three magnetic-field induced heteronuclear Feshbach resonances were identified in collisions between bosonic 87Rb and fermionic 40K atoms in their absolute ground states. Strong inelastic loss from ...an optically trapped mixture was observed at the resonance positions of 492, 512, and 543+/-2 G. The magnetic-field locations of these resonances place a tight constraint on the triplet and singlet cross-species scattering lengths, yielding (-281+/-15)a(0) and (-54+/-12)a(0), respectively. The width of the loss feature at 543 G is 3.7+/-1.5 G wide; this broad Feshbach resonance should enable experimental control of the interspecies interactions.
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CMK, CTK, FMFMET, IJS, NUK, PNG, UM
Reef-building corals live in symbiosis with a diverse range of dinoflagellate algae (genus Symbiodinium) that differentially influence the fitness of the coral holobiont. The comparative role of ...symbiont type in holobiont fitness in relation to host genotype or the environment, however, is largely unknown. We addressed this knowledge gap by manipulating host-symbiont combinations and comparing growth, survival and thermal tolerance among the resultant holobionts in different environments.
Offspring of the coral, Acropora millepora, from two thermally contrasting locations, were experimentally infected with one of six Symbiodinium types, which spanned three phylogenetic clades (A, C and D), and then outplanted to the two parental field locations (central and southern inshore Great Barrier Reef, Australia). Growth and survival of juvenile corals were monitored for 31-35 weeks, after which their thermo-tolerance was experimentally assessed. Our results showed that: (1) Symbiodinium type was the most important predictor of holobiont fitness, as measured by growth, survival, and thermo-tolerance; (2) growth and survival, but not heat-tolerance, were also affected by local environmental conditions; and (3) host population had little to no effect on holobiont fitness. Furthermore, coral-algal associations were established with symbiont types belonging to clades A, C and D, but three out of four symbiont types belonging to clade C failed to establish a symbiosis. Associations with clade A had the lowest fitness and were unstable in the field. Lastly, Symbiodinium types C1 and D were found to be relatively thermo-tolerant, with type D conferring the highest tolerance in A. millepora.
These results highlight the complex interactions that occur between the coral host, the algal symbiont, and the environment to shape the fitness of the coral holobiont. An improved understanding of the factors affecting coral holobiont fitness will assist in predicting the responses of corals to global climate change.
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DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Rett syndrome (RTT) is a rare, X-linked neurodevelopmental disorder typically affecting females, resulting in a range of symptoms including autistic features, intellectual impairment, motor ...deterioration, and autonomic abnormalities. RTT is primarily caused by the genetic mutation of the Mecp2 gene. Initially considered a neuronal disease, recent research shows that glial dysfunction contributes to the RTT disease phenotype. In the following manuscript, we review the evidence regarding glial dysfunction and its effects on disease etiology.
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IZUM, KILJ, NUK, PILJ, PNG, SAZU, UL, UM, UPUK
Progressive supranuclear palsy (PSP) is a progressive adult-onset neurodegenerative disease. Abnormally, phosphorylated forms of the microtubule-associated protein tau containing four repeat domains ...(4R-tau) aggregate in neurons. Additionally, increasing evidence suggests that secretion and uptake of fragments of abnormal 4R-tau may play a role in disease progression. This extracellular tau is a natural target for immunotherapy.
Three monoclonal antibodies targeting extracellular tau are in clinical stages of development. ABBV-8E12 and BIIB092 were safe in Phase 1, but both Phase two studies recently failed futility analyses. UCB0107 recently reported (in abstract form) Phase 1 safety results, and a Phase 2 study is under consideration. Stem cell therapy and the infusion of plasma are also being explored clinically.
The likely role of extracellular tau in the progression of PSP makes tau a natural target for targeted immunotherapy. Clinical trials are still in early stages, and although tau immunotherapy has largely been shown to be safe, efficacy has yet to be demonstrated.
Anti-Müllerian hormone (Amh) is in mammals known as a TGFβ type of glycoprotein processed to yield a bioactive C-terminal homodimer that directs regression of Müllerian ducts in the male fetus and ...regulates steroidogenesis and early stages of folliculogenesis. Here, we report on the zebrafish Amh homologue. Zebrafish, as all teleost fish, do not have Müllerian ducts. Antibodies raised against the N- and C-terminal part of Amh were used to study the processing of endogenous and recombinant Amh. The N-terminally directed antibody detected a 27-kDa protein, whereas the C-terminally directed one recognized a 32-kDa protein in testes extracts, both apparently not glycosylated. The C-terminal fragment was present as a monomeric protein, because reducing conditions did not change its apparent molecular mass. Recombinant zebrafish Amh was cleaved with plasmin to N- and C-terminal fragments that after deglycosylation were similar in size to endogenous Amh fragments. Mass spectrometry and N-terminal sequencing revealed a 21-residue N-terminal leader sequence and a plasmin cleavage site after Lys or Arg within Lys-Arg-His at position 263–265, which produce theoretical fragments in accordance with the experimental results. Experiments using adult zebrafish testes tissue cultures showed that plasmin-cleaved, but not uncleaved, Amh inhibited gonadotropin-stimulated androgen production. However, androgens did not modulate amh expression that was, on the other hand, down-regulated by Fsh. Moreover, plasmin-cleaved Amh inhibited androgen-stimulated proliferation as well as differentiation of type A spermatogonia. In conclusion, zebrafish Amh is processed to become bioactive and has independent functions in inhibiting both steroidogenesis and spermatogenesis.
Background: A self-rating inventory has been developed to measure DSM-IV and ICD-10 diagnoses of major (moderate to severe) depression by the patients’ self-reported symptoms. This Major Depression ...Inventory (MDI) can be scored both according to the DSM-IV and the ICD-10 algorithms for depressive symptomatology and according to severity scales by the simple total sum of the items.
Methods: The Schedule for Clinical Assessment in Neuropsychiatry (SCAN) was used as index of validity for the clinician’s DSM-IV and ICD-10 diagnosis of major (moderate to severe) depression. The sensitivity and specificity of MDI was assessed in a sample of 43 subjects covering a spectrum of depressive symptoms.
Results: The sensitivity of the MDI algorithms for major depression varied between 0.86 and 0.92. The specificity varied between 0.82 and 0.86. When using the total score of MDI the optimal cut-off score was estimated 26 and the total score was shown to be a sufficient statistic.
Limitations: The sample of subjects was limited. Patients with psychotic depression were not included.
Conclusion: The MDI was found to have a sensitivity and specificity which is acceptable. The questionnaire is brief and can be scored diagnostically by the DSM-IV and ICD-10 algorithms as well as by its simple total score.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UL, UM, UPCLJ, UPUK
Objective
To evaluate whether human epididymis protein 4 (HE4) and CA125 correlate with known high‐risk prognostic factors for endometrial cancer.
Design
Prospective multicenter study.
Setting
Three ...Danish tertiary gynecological oncology centers.
Population
A total of 352 patients with endometrial cancer and atypical endometrial hyperplasia consecutively referred between 1 September 2009 and 1 January 2012.
Methods
Preoperative blood samples were obtained from all patients. Biomarker levels were correlated with pathological characteristics of hysterectomy specimens.
Main outcome measures
FIGO stage, depth of myometrial invasion, cervical involvement, lymph node metastases, and histological type and grade of tumor.
Results
We found that both HE4 and CA125 were significantly positively correlated with histological grade (HE4: p = 0.002 and CA125: p = 0.027), lymph node metastases (HE4: p = 0.013 and CA125: p < 0.0001), myometrial invasion (p < 0.0001) and cervical involvement (p < 0.0001). Furthermore, a significant increase was found with increasing FIGO stage for both markers (p < 0.0001). In a combined index including age, the diagnostic value increases. Area under the receiver operating characteristics curves were higher for the index compared with the markers individually for all our endpoints. The calculated plots for the combined index may assist gynecologists in predicting the risk of deep myometrial invasion, cervical involvement and lymph node metastases. The analyses emphasize that the combined markers should be used in the prediction of prognostic factors.
Conclusion
This study confirmed that the markers are significantly elevated in patients with prognostic high‐risk factors and may, therefore, be used as an additional tool in combination with imaging and clinical information when planning the treatment of endometrial cancer patients.
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BFBNIB, FZAB, GIS, IJS, KILJ, NLZOH, NUK, OILJ, SBCE, SBMB, UL, UM, UPUK
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