UX Orionis stars (UXors) are Herbig Ae/Be or T Tauri stars exhibiting sporadic occultation of stellar light by circumstellar dust. GM Cephei is such a UXor in the young (∼4 Myr) open cluster Trumpler ...37, showing prominent infrared excess, emission-line spectra, and flare activity. Our photometric monitoring (2008-2018) detects (1) an ∼3.43 day period, likely arising from rotational modulation by surface starspots, (2) sporadic brightening on timescales of days due to accretion, (3) irregular minor flux drops due to circumstellar dust extinction, and (4) major flux drops, each lasting for a couple of months with a recurrence time, though not exactly periodic, of about two years. The star experiences normal reddening by large grains, i.e., redder when dimmer, but exhibits an unusual "blueing" phenomenon in that the star turns blue near brightness minima. The maximum extinction during relatively short (lasting ≤50 days) events, is proportional to the duration, a consequence of varying clump sizes. For longer events, the extinction is independent of duration, suggestive of a transverse string distribution of clumps. Polarization monitoring indicates an optical polarization varying ∼3%-8%, with the level anticorrelated with the slow brightness change. Temporal variation of the unpolarized and polarized light sets constraints on the size and orbital distance of the circumstellar clumps in the interplay with the young star and scattering envelope. These transiting clumps are edge-on manifestations of the ring- or spiral-like structures found recently in young stars with imaging in infrared of scattered light, or in submillimeter of thermalized dust emission.
Relative Risk (
), Hazard Ratio (
), and Odds Ratio (
) are commonly used statistical measures in the field of public health to assess the magnitude of the effect of exposure factors on outcomes. ...These indicators have different calculation principles and implications in public health. However, a few researchers misused or misinterpreted
,
, and
values when interpreting study results. Therefore, this article explores the relationships and differences among these measures, as well as the correct selection and application of
,
, and
in both cohort study and case-control study.
Abstract Introduction The multinucleated syncytiotrophoblast is formed and maintained by cytotrophoblast cell fusion and serves multiple functions to ensure a successful pregnancy. We have previously ...reported that the proprotein convertase furin is required for trophoblast syncytialization by processing type 1 insulin-like growth factor receptor (IGF1R). Methods Utilizing trophoblast cell fusion models including induced fusion of choriocarcinoma BeWo cells and spontaneous fusion of primary cultured term cytotrophoblast cells, the expression of furin was evaluated by quantitative real-time PCR, Western blotting and immunofluorescence. The key transcription factor regulating the FUR gene promoter and critical responsive elements were identified by luciferase reporter assays, truncated mutants analysis, site-directed mutagenesis and ChIP. Results We demonstrated that the levels of FUR mRNA were significantly stimulated by cAMP/PKA signaling pathway during spontaneous fusion of cytotrophoblast cells and forskolin-induced fusion of BeWo cells. cAMP-responsive element binding protein (CREB) was proven to be the key transcription factor which regulated the FUR P1 promoter during forskolin-induced BeWo cell fusion, and two critical cAMP-responsive elements (CREs) in the P1 promoter were further identified. Finally, we showed that CREB mediated endogenous furin activation and that CREB siRNA attenuated forskolin-induced furin expression and cell fusion in BeWo cells. Discussion This provides the first evidence of the upstream regulator of furin during trophoblast cell fusion. Conclusions The above results suggest that the FUR transcription is activated by CREB-dependent stimulation of the FUR P1 promoter during human trophoblast syncytialization.
Mutations in six genes have been associated with achromatopsia (ACHM): CNGA3, CNGB3, PDE6H, PDE6C, GNAT2, and ATF6. ATF6 is the most recent gene to be identified, though thorough phenotyping of this ...genetic subtype is lacking. Here, we sought to test the hypothesis that ATF6-associated ACHM is a structurally distinct form of congenital ACHM.
Seven genetically confirmed subjects from five nonconsanguineous families were recruited. Foveal hypoplasia and the integrity of the ellipsoid zone (EZ) band (a.k.a., IS/OS) were graded from optical coherence tomography (OCT) images. Images of the photoreceptor mosaic were acquired using confocal and nonconfocal split-detection adaptive optics scanning light ophthalmoscopy (AOSLO). Parafoveal cone and rod density values were calculated and compared to published normative data as well as data from two subjects harboring CNGA3 or CNGB3 mutations who were recruited for comparative purposes. Additionally, nonconfocal dark-field AOSLO images of the retinal pigment epithelium were obtained, with quantitative analysis performed in one subject with ATF6-ACHM.
Foveal hypoplasia was observed in all subjects with ATF6 mutations. Absence of the EZ band within the foveal region (grade 3) or appearance of a hyporeflective zone (grade 4) was seen in all subjects with ATF6 using OCT. There was no evidence of remnant foveal cone structure using confocal AOSLO, although sporadic cone-like structures were seen in nonconfocal split-detection AOSLO. There was a lack of cone structure in the parafovea, in direct contrast to previous reports.
Our data demonstrate a near absence of cone structure in subjects harboring ATF6 mutations. This implicates ATF6 as having a major role in cone development and suggests that at least a subset of subjects with ATF6-ACHM have markedly fewer cellular targets for cone-directed gene therapies than do subjects with CNGA3- or CNGB3-ACHM.
Introduction: Itch is a distressing atopic dermatitis (AD) symptom that impacts quality of life. With the emergence of multiple new agents for the treatment of AD, the ability and speed with which an ...agent reduces itch may factor in agent selection.
Objective: In this study, the primary objective was to quantify the rate at which agents for AD provide itch reduction using the peak itch numerical rating scale (NRS) data from phase II and III clinical trials.
Methods: A PubMed literature search was performed in February 2020 to find phase II and III randomized clinical trials for the treatment of AD published from 2014 to 2020. A TIMEACLIR-Itch value was calculated from NRS data to represent the time to meaningful itch reduction.
Results: We find a shorter TIme to achieving a MEAningful CLInical Response for itch reduction (TIMEACLIR-Itch) for small molecule inhibitors when compared to biologic agents. We also observe that nemolizumab achieves TIMEACLIR-Itch more quickly than IL-4 or IL-4/13 agents.
Conclusion: These findings support the role that IL-31 has in producing itch and the role Janus kinase inhibitors (JAKinibs) play in itch reduction. This comparison of TIMEACLIR-Itch for different treatments may help guide therapy and management for AD patients.
Abstract
Aims
Despite being an essential therapy for breast cancer, trastuzumab has potential risks of cardiotoxicity. The incidence of trastuzumab-related major adverse cardiac and cerebrovascular ...event (MACCE) and its predictors remain unknown in Taiwan.
Methods and results
Through a three-hospital retrospective cohort study, we analyzed the incidence of MACCE in 386 breast cancer patients exposure to trastuzumab from 2010 to 2018. To further reconfirm our findings, in a nationwide study using the Taiwanese National Health Insurance Research Database and National Cancer Registry, we identified 13502 women diagnosed with breast cancer who received chemotherapy from 2010 to 2015 and found 6751 women who received initial treatment with trastuzumab. After 1:1 propensity score matching with trastuzumab nonusers, the incidence of MACCE was measured with a median follow-up of 36 months. In the hospital-based study, among 386 patients receiving trastuzumab, the 5-year incidences of MACCE and heart failure (HF) were 5.4% and 2.8%, respectively. In the national cohort, the crude incidences of MACCEs and HF were 4.67% and 3.21%, respectively. After adjustment for age and comorbidities, the hazard ratio of MACCE was 1.485 (95% CI 1.246–1.769). Notably, among the endpoints, only the hazard ratio of HF was significantly higher in patients receiving trastuzumab than in nonusers. In the subgroup analysis, except for patients also using taxanes, those receiving trastuzumab had a higher risk of MACCE than nonusers.
Conclusions
From clinical observations in a nationwide cohort, we found an increased risk of MACCE, especially HF, in patients receiving trastuzumab. Given that its cardiotoxicity is independent of traditional cardiovascular risks, our findings highlight critical concerns regarding the cardiac safety of trastuzumab use.
Funding Acknowledgement
Type of funding sources: Private hospital(s). Main funding source(s): Chi-Mei Medical Center, National Cheng Kung University Hospital
High precision, L sub 2.3 -edge photoabsorption and magnetic circular dichroism spectra of iron and cobalt were measured in transmission with in situ grown thin films, eliminating experimental ...artifacts encountered by the indirect methods used in all previous measurements. The magnetic moments determined from the integrals of these spectra are found to be excellent agreement (within 3%) for the orbital to spin moment ratios, and in good agreement (within 7%) for the individual moments, with those obtained from Einstein-de Haas gyromagnetic ratio measurements, demonstrating decisively the applicability of the individual orbital and spin sum rules.
Zika virus (ZIKV) was first isolated in Africa; decades later, caused large outbreaks in the Pacific, and is considered endemic in Asia. We aim to describe ZIKV disease epidemiology outside the ...Americas, the importance of travelers as sentinels of disease transmission, and discrepancies in travel advisories from major international health organizations.
This descriptive analysis using GeoSentinel Surveillance Network records involves sixty-four travel and tropical medicine clinics in 29 countries. Ill returned travelers with a confirmed or probable diagnosis of ZIKV disease acquired in Africa, Asia and the Pacific seen between 1 January 2012 and 31 December 2016 are included, and the frequencies of demographic, trip, and diagnostic characteristics described. ZIKV was acquired in Asia (18), the Pacific (10) and Africa (1). For five countries (Indonesia, Philippines, Thailand, Vietnam, Cameroon), GeoSentinel patients were sentinel markers of recent Zika activity. Additionally, the first confirmed ZIKV infection acquired in Kiribati was reported to GeoSentinel (2015), and a probable case was reported from Timor Leste (April 2016), representing the only case known to date. Review of Zika situation updates from major international health authorities for country risk classifications shows heterogeneity in ZIKV country travel advisories.
Travelers are integral to the global spread of ZIKV, serving as sentinel markers of disease activity. Although GeoSentinel data are collected by specialized clinics and do not capture all imported cases, we show that surveillance of imported infections by returned travelers augments local surveillance system data regarding ZIKV epidemiology and can assist with risk categorization by international authorities. However, travel advisories are variable due to risk uncertainties.
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