| 1. |
- Ishigaki, Kazuyoshi, et al.
(author)
-
Multi-ancestry genome-wide association analyses identify novel genetic mechanisms in rheumatoid arthritis
- 2022
-
In: Nature Genetics. - : Springer Nature. - 1061-4036 .- 1546-1718. ; 54:11, s. 1640-1651
-
Journal article (peer-reviewed)abstract
- Rheumatoid arthritis (RA) is a highly heritable complex disease with unknown etiology. Multi-ancestry genetic research of RA promises to improve power to detect genetic signals, fine-mapping resolution and performances of polygenic risk scores (PRS). Here, we present a large-scale genome-wide association study (GWAS) of RA, which includes 276,020 samples from five ancestral groups. We conducted a multi-ancestry meta-analysis and identified 124 loci (P < 5 × 10−8), of which 34 are novel. Candidate genes at the novel loci suggest essential roles of the immune system (for example, TNIP2 and TNFRSF11A) and joint tissues (for example, WISP1) in RA etiology. Multi-ancestry fine-mapping identified putatively causal variants with biological insights (for example, LEF1). Moreover, PRS based on multi-ancestry GWAS outperformed PRS based on single-ancestry GWAS and had comparable performance between populations of European and East Asian ancestries. Our study provides several insights into the etiology of RA and improves the genetic predictability of RA.
|
|
| 2. |
- Klionsky, Daniel J., et al.
(author)
-
Guidelines for the use and interpretation of assays for monitoring autophagy
- 2012
-
In: Autophagy. - : Informa UK Limited. - 1554-8635 .- 1554-8627. ; 8:4, s. 445-544
-
Research review (peer-reviewed)abstract
- In 2008 we published the first set of guidelines for standardizing research in autophagy. Since then, research on this topic has continued to accelerate, and many new scientists have entered the field. Our knowledge base and relevant new technologies have also been expanding. Accordingly, it is important to update these guidelines for monitoring autophagy in different organisms. Various reviews have described the range of assays that have been used for this purpose. Nevertheless, there continues to be confusion regarding acceptable methods to measure autophagy, especially in multicellular eukaryotes. A key point that needs to be emphasized is that there is a difference between measurements that monitor the numbers or volume of autophagic elements (e.g., autophagosomes or autolysosomes) at any stage of the autophagic process vs. those that measure flux through the autophagy pathway (i.e., the complete process); thus, a block in macroautophagy that results in autophagosome accumulation needs to be differentiated from stimuli that result in increased autophagic activity, defined as increased autophagy induction coupled with increased delivery to, and degradation within, lysosomes (in most higher eukaryotes and some protists such as Dictyostelium) or the vacuole (in plants and fungi). In other words, it is especially important that investigators new to the field understand that the appearance of more autophagosomes does not necessarily equate with more autophagy. In fact, in many cases, autophagosomes accumulate because of a block in trafficking to lysosomes without a concomitant change in autophagosome biogenesis, whereas an increase in autolysosomes may reflect a reduction in degradative activity. Here, we present a set of guidelines for the selection and interpretation of methods for use by investigators who aim to examine macroautophagy and related processes, as well as for reviewers who need to provide realistic and reasonable critiques of papers that are focused on these processes. These guidelines are not meant to be a formulaic set of rules, because the appropriate assays depend in part on the question being asked and the system being used. In addition, we emphasize that no individual assay is guaranteed to be the most appropriate one in every situation, and we strongly recommend the use of multiple assays to monitor autophagy. In these guidelines, we consider these various methods of assessing autophagy and what information can, or cannot, be obtained from them. Finally, by discussing the merits and limits of particular autophagy assays, we hope to encourage technical innovation in the field.
|
|
| 3. |
|
|
| 4. |
- Kamae, Tuneyoshi, et al.
(author)
-
PoGOLite - A high sensitivity balloon-borne soft gamma-ray polarimeter
- 2008
-
In: Astroparticle physics. - : Elsevier BV. - 0927-6505 .- 1873-2852. ; 30:2, s. 72-84
-
Journal article (peer-reviewed)abstract
- We describe a new balloon-borne instrument (PoGOLite) capable of detecting 10% polarisation from 200 mCrab point-like sources between 25 and 80 keV in one 6-h flight. Polarisation measurements in the soft gamma-ray band are expected to provide a powerful probe into high energy emission mechanisms as well as the distribution of magnetic fields, radiation fields and interstellar matter. Synchrotron radiation, inverse Compton scattering and propagation through high magnetic fields are likely to produce high degrees of polarisation in the energy band of the instrument. We demonstrate, through tests at accelerators, with radioactive sources and through computer simulations, that PoGOLite will be able to detect degrees of polarisation as predicted by models for several classes of high energy sources. At present, only exploratory polarisation measurements have been carried out in the soft gamma-ray band. Reduction of the large background produced by cosmic-ray particles while securing a large effective area has been the greatest challenge. PoGOLite uses Compton scattering and photo-absorption in an array of 217 well-type phoswich detector cells made of plastic and BGO scintillators surrounded by a BGO anticoincidence shield and a thick polyethylene neutron shield. The narrow Held of view (FWHM = 1.25 msr, 2.0 deg x 2.0 deg) obtained with detector cells and the use of thick background shields warrant a large effective area for polarisation measurements (similar to 228 cm(2) at E = 40 keV) without sacrificing the signal-to-noise ratio. Simulation studies for an atmospheric overburden of 3-4 g/cm(2) indicate that neutrons and gamma-rays entering the PDC assembly through the shields are dominant backgrounds. Off-line event selection based on recorded phototube waveforms and Compton kinematics reduce the background to that expected for a similar to 100 mCrab source between 25 and 50 keV. A 6-h observation of the Crab pulsar will differentiate between the Polar Cap/Slot Gap, Outer Gap, and Caustic models with greater than 5 sigma significance; and also cleanly identify the Compton reflection component in the Cygnus X-1 hard state. Long-duration flights will measure the dependence of the polarisation across the cyclotron absorption line in Hercules X-1. A scaled-down instrument will be flown as a pathfinder mission from the north of Sweden in 2010. The first science flight is planned to take place shortly thereafter.
|
|
| 5. |
|
|
| 6. |
- Menzies, Scott W, et al.
(author)
-
Dermoscopic Evaluation of Nodular Melanoma.
- 2013
-
In: JAMA dermatology (Chicago, Ill.). - : American Medical Association (AMA). - 2168-6084 .- 2168-6068. ; 149:6, s. 699-709
-
Journal article (peer-reviewed)abstract
- IMPORTANCE Nodular melanoma (NM) is a rapidly progressing potentially lethal skin tumor for which early diagnosis is critical. OBJECTIVE To determine the dermoscopy features of NM. DESIGN Eighty-three cases of NM, 134 of invasive non-NM, 115 of nodular benign melanocytic tumors, and 135 of nodular nonmelanocytic tumors were scored for dermoscopy features using modified and previously described methods. Lesions were separated into amelanotic/hypomelanotic or pigmented to assess outcomes. SETTING Predominantly hospital-based clinics from 5 continents. MAIN OUTCOME MEASURES Sensitivity, specificity, and odds ratios for features/models for the diagnosis of melanoma. RESULTS Nodular melanoma occurred more frequently as amelanotic/hypomelanotic (37.3%) than did invasive non-NM (7.5%). Pigmented NM had a more frequent (compared with invasive non-NM; in descending order of odds ratio) symmetrical pigmentation pattern (5.8% vs 0.8%), large-diameter vessels, areas of homogeneous blue pigmentation, symmetrical shape, predominant peripheral vessels, blue-white veil, pink color, black color, and milky red/pink areas. Pigmented NM less frequently displayed an atypical broadened network, pigment network or pseudonetwork, multiple blue-gray dots, scarlike depigmentation, irregularly distributed and sized brown dots and globules, tan color, irregularly shaped depigmentation, and irregularly distributed and sized dots and globules of any color. The most important positive correlating features of pigmented NM vs nodular nonmelanoma were peripheral black dots/globules, multiple brown dots, irregular black dots/globules, blue-white veil, homogeneous blue pigmentation, 5 to 6 colors, and black color. A model to classify a lesion as melanocytic gave a high sensitivity (>98.0%) for both nodular pigmented and nonnodular pigmented melanoma but a lower sensitivity for amelanotic/hypomelanotic NM (84%). A method for diagnosing amelanotic/hypomelanotic malignant lesions (including basal cell carcinoma) gave a 93% sensitivity and 70% specificity for NM. CONCLUSIONS AND RELEVANCE When a progressively growing, symmetrically patterned melanocytic nodule is identified, NM needs to be excluded.
|
|
| 7. |
- Russo, Teresa, et al.
(author)
-
Indications for Digital Monitoring of Patients With Multiple Nevi: Recommendations from the International Dermoscopy Society
- 2022
-
In: Dermatology Practical and Conceptual. - : Mattioli1885. - 2160-9381. ; 12
-
Journal article (peer-reviewed)abstract
- Introduction: In patients with multiple nevi, sequential imaging using total body skin photography (TBSP) coupled with digital dermoscopy (DD) documentation reduces unnecessary excisions and improves the early detection of melanoma. Correct patient selection is essential for optimizing the efficacy of this diagnostic approach. Objectives: The purpose of the study was to identify, via expert consensus, the best indications for TBSP and DD follow-up. Methods: This study was performed on behalf of the International Dermoscopy Society (IDS). We attained consensus by using an e-Delphi methodology. The panel of participants included international experts in dermoscopy. In each Delphi round, experts were asked to select from a list of indications for TBSP and DD. Results: Expert consensus was attained after 3 rounds of Delphi. Participants considered a total nevus count of 60 or more nevi or the presence of a CDKN2A mutation sufficient to refer the patient for digital monitoring. Patients with more than 40 nevi were only considered an indication in case of personal history of melanoma or red hair and/or a MC1R mutation or history of organ transplantation. Conclusions: Our recommendations support clinicians in choosing appropriate follow-up regimens for patients with multiple nevi and in applying the time-consuming procedure of sequential imaging more efficiently. Further studies and real-life data are needed to confirm the usefulness of this list of indications in clinical practice.
|
|
| 8. |
- Tiodorovic, Danica, et al.
(author)
-
Dermatoscopic patterns of cutaneous metastases: A multicentre cross-sectional study of the International Dermoscopy Society
- 2024
-
In: JOURNAL OF THE EUROPEAN ACADEMY OF DERMATOLOGY AND VENEREOLOGY. - 0926-9959 .- 1468-3083.
-
Journal article (peer-reviewed)abstract
- BackgroundThe detection of cutaneous metastases (CMs) from various primary tumours represents a diagnostic challenge.ObjectivesOur aim was to evaluate the general characteristics and dermatoscopic features of CMs from different primary tumours.MethodsRetrospective, multicentre, descriptive, cross-sectional study of biopsy-proven CMs.ResultsWe included 583 patients (247 females, median age: 64 years, 25%-75% percentiles: 54-74 years) with 632 CMs, of which 52.2% (n = 330) were local, and 26.7% (n = 169) were distant. The most common primary tumours were melanomas (n = 474) and breast cancer (n = 59). Most non-melanoma CMs were non-pigmented (n = 151, 95.6%). Of 169 distant metastases, 54 (32.0%) appeared on the head and neck region. On dermatoscopy, pigmented melanoma metastases were frequently structureless blue (63.6%, n = 201), while amelanotic metastases were typified by linear serpentine vessels and a white structureless pattern. No significant difference was found between amelanotic melanoma metastases and CMs of other primary tumours.ConclusionsThe head and neck area is a common site for distant CMs. Our study confirms that most pigmented melanoma metastasis are structureless blue on dermatoscopy and may mimic blue nevi. Amelanotic metastases are typified by linear serpentine vessels and a white structureless pattern, regardless of the primary tumour.
|
|
