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1.
Isis Gayed M Farahnaz Eskandari Peter McLaughlin Barbara Pro Roxana Diba Bita Esmaeli 《Ophthalmic surgery, lasers & imaging》2007,38(4):319-325
BACKGROUND AND OBJECTIVE: An observational case series to assess the value of positron emission tomography (PET) in staging ocular adnexal lymphomas and evaluating their response to therapy. PATIENTS AND METHODS: The clinical records of 16 consecutive patients with ocular adnexal lymphoma for whom pretreatment and posttreatment PET scans and corresponding computed tomography (CT) and magnetic resonance imaging (MRI) scans were available were compared. RESULTS: Pretreatment PET scans demonstrated fluorine 18-fluorodeoxyglucose (FDG) positive lesions in 15 orbits of 12 patients. In 1 patient with low-grade follicular lymphoma of the orbit, PET revealed an additional focus of lymphoma in the deltoid muscle that was missed on clinical examination and conventional radiography. All of the posttreatment PET scans showed complete resolution of FDG uptake, suggesting good response to therapy. However, posttreatment CT and MRI scans demonstrated residual masses in 3 patients. CONCLUSIONS: PET is valuable for initial staging of ocular adnexal lymphomas and may be a good adjunct to conventional imaging in evaluation of response to therapy. 相似文献
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Shobana Sekar Livia Tomasini Christos Proukakis Taejeong Bae Logan Manlove Yeongjun Jang Soraya Scuderi Bo Zhou Maria Kalyva Anahita Amiri Jessica Mariani Fritz J. Sedlazeck Alexander E. Urban Flora M. Vaccarino Alexej Abyzov 《Genome research》2020,30(12):1695
Somatic mosaicism, manifesting as single nucleotide variants (SNVs), mobile element insertions, and structural changes in the DNA, is a common phenomenon in human brain cells, with potential functional consequences. Using a clonal approach, we previously detected 200–400 mosaic SNVs per cell in three human fetal brains (15–21 wk postconception). However, structural variation in the human fetal brain has not yet been investigated. Here, we discover and validate four mosaic structural variants (SVs) in the same brains and resolve their precise breakpoints. The SVs were of kilobase scale and complex, consisting of deletion(s) and rearranged genomic fragments, which sometimes originated from different chromosomes. Sequences at the breakpoints of these rearrangements had microhomologies, suggesting their origin from replication errors. One SV was found in two clones, and we timed its origin to ∼14 wk postconception. No large scale mosaic copy number variants (CNVs) were detectable in normal fetal human brains, suggesting that previously reported megabase-scale CNVs in neurons arise at later stages of development. By reanalysis of public single nuclei data from adult brain neurons, we detected an extrachromosomal circular DNA event. Our study reveals the existence of mosaic SVs in the developing human brain, likely arising from cell proliferation during mid-neurogenesis. Although relatively rare compared to SNVs and present in ∼10% of neurons, SVs in developing human brain affect a comparable number of bases in the genome (∼6200 vs. ∼4000 bp), implying that they may have similar functional consequences.Somatic mosaicism, the presence of more than one genotype in the somatic cells of an individual, is a prominent phenomenon in the human central nervous system. Forms of mosaicism include aneuploidies and smaller copy number variants (CNVs), structural variants (SVs), mobile element insertions, indels, and single nucleotide variants (SNVs). The developing human brain exhibits high levels of aneuploidy compared to other tissues, generating genetic diversity in neurons (Pack et al. 2005; Yurov et al. 2007; Bushman and Chun 2013). Such aneuploidy was suggested to be a natural feature of neurons, rather than a distinctive feature of neurodegeneration. However, the frequency of aneuploidy in neurons has been debated, with a separate study suggesting that aneuploidies occur in only about 2.2% of mature adult neurons (Knouse et al. 2014). They hence infer that such aneuploidy could have adverse effects at the cellular and organismal levels. Additionally, analysis of single cells from normal and pathological human brains identified large, private, and likely clonal somatic CNVs in both normal and diseased brains (Gole et al. 2013; McConnell et al. 2013; Cai et al. 2014; Knouse et al. 2016; Chronister et al. 2019; Perez-Rodriguez et al. 2019), with 3%–25% of human cerebral cortical nuclei carrying megabase-scale CNVs (Chronister et al. 2019) and deletions being twice as common as duplications (McConnell et al. 2013). Given that CNVs often arise from nonhomologous recombination and replication errors, their likely time of origin is during brain development. However, when CNVs first arise in human brain development has not yet been investigated. The present work is the first to examine this question using clonal populations of neuronal progenitor cells (NPCs) obtained from fetal human brains.Detection of CNVs in single neurons is challenging, given the need to amplify DNA. Such amplification may introduce artifacts that could, in turn, be misinterpreted as CNVs. In order to address this technical limitation, Hazen et al. reprogrammed adult postmitotic neurons using somatic cell nuclear transfer (SCNT) of neuronal nuclei into enucleated oocytes (Hazen et al. 2016). These oocytes then made sufficient copies of the neuronal genome allowing for whole-genome sequencing (WGS), thus eliminating the need for amplification in vitro. Using this method, they identified a total of nine structural variants in six neurons from mice, three of which were complex rearrangements. However, it is not possible to extend such studies to humans, given the ethical issues involved, besides the technical challenges in obtaining and cloning adult neurons. To circumvent the need of single-cell DNA amplification or nuclear cloning, we examined clonal cell populations obtained from neural progenitor cells from the frontal region of the cerebral cortex (FR), parietal cortex (PA) and basal ganglia (BG) and describe here the discovery and analysis of mosaic SVs in these NPCs (Bae et al. 2018). These clones were sequenced at 30× coverage (much higher than most previous single-cell studies), allowing identification of SVs other than large deletions and duplications as well as precise breakpoint resolution. 相似文献
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Rania El Fekih James Hurley Vasisht Tadigotla Areej Alghamdi Anand Srivastava Christine Coticchia John Choi Hazim Allos Karim Yatim Juliano Alhaddad Siawosh Eskandari Philip Chu Albana B. Mihali Isadora T. Lape Mauricio P. Lima Filho Bruno T. Aoyama Anil Chandraker Kassem Safa James F. Markmann Leonardo V. Riella Richard N. Formica Johan Skog Jamil R. Azzi 《Journal of the American Society of Nephrology : JASN》2021,32(4):994
BackgroundDeveloping a noninvasive clinical test to accurately diagnose kidney allograft rejection is critical to improve allograft outcomes. Urinary exosomes, tiny vesicles released into the urine that carry parent cells’ proteins and nucleic acids, reflect the biologic function of the parent cells within the kidney, including immune cells. Their stability in urine makes them a potentially powerful tool for liquid biopsy and a noninvasive diagnostic biomarker for kidney-transplant rejection.MethodsUsing 192 of 220 urine samples with matched biopsy samples from 175 patients who underwent a clinically indicated kidney-transplant biopsy, we isolated urinary exosomal mRNAs and developed rejection signatures on the basis of differential gene expression. We used crossvalidation to assess the performance of the signatures on multiple data subsets.ResultsAn exosomal mRNA signature discriminated between biopsy samples from patients with all-cause rejection and those with no rejection, yielding an area under the curve (AUC) of 0.93 (95% CI, 0.87 to 0.98), which is significantly better than the current standard of care (increase in eGFR AUC of 0.57; 95% CI, 0.49 to 0.65). The exosome-based signature’s negative predictive value was 93.3% and its positive predictive value was 86.2%. Using the same approach, we identified an additional gene signature that discriminated patients with T cell–mediated rejection from those with antibody-mediated rejection (with an AUC of 0.87; 95% CI, 0.76 to 0.97). This signature’s negative predictive value was 90.6% and its positive predictive value was 77.8%.ConclusionsOur findings show that mRNA signatures derived from urinary exosomes represent a powerful and noninvasive tool to screen for kidney allograft rejection. This finding has the potential to assist clinicians in therapeutic decision making. 相似文献
5.
Anahita Jalilvand Katelyn A. Levene Kejal Shah Bradley Needleman Sabrena F. Noria 《Surgery for obesity and related diseases》2021,17(5):921-930
BackgroundStudies on early postoperative readmissions after bariatric surgery (BS) have examined readmissions as a single entity, regardless of urgency. Strategies to lower nonurgent readmissions would reduce unnecessary hospital utilization.ObjectivesTo identify predictors of urgent readmissions (UR) versus nonurgent readmissions (NUR) at 30 days post-BS.SettingSingle academic institution.MethodsPatients undergoing primary BS over 2 years (n = 589) were retrospectively reviewed. Baseline demographic, medical, and hospitalization data were compared between readmitted patients, stratified by urgency, and nonreadmitted patients. Multivariate regression models of UR and NUR were created using variables with a P value ≤ .2 on univariate analyses. A P value ≤ .05 was considered statistically significant.ResultsThere were 39 documented instances of 30-day readmissions, of which 44% (n = 17) were NUR; NUR patients were more likely to be female (100% versus 78.2% male; P = .03) and trended toward being younger, experiencing ≥2 perioperative complications, and having a longer index hospital length of stay (LOS). Patients with URs had a higher baseline BMI (52.5 ± 11.4 kg/m2 versus 48.7 ± 8.3 kg/m2, respectively; P = .04), were more likely to have sleep apnea (77.3% versus 56.1%, respectively; P = .05), had a longer LOS (3 versus 2 d, respectively; P = .007), and were more likely to have ≥2 postoperative complications (46% versus 17.0%, respectively; P = .003) compared with those with an NUR. Independent predictors of NUR included public insurance (odds ratio [OR] = 3.7; 95% confidence interval [CI], 1.17–11.67; P = .03), younger age (OR = 1.05; 95% CI, 1–1.01; P = .04), and female sex, while URs were independently predicted by LOS (OR = 1.3; 95% CI, 1.04–1.5; P = .02).ConclusionsPublic insurance appears to be associated with NURs, while LOS predicts URs after BS. This suggests an important dichotomy within readmissions based on urgency, which has important implications for targeted quality initiatives. 相似文献
6.
Sprengel deformity is a rare orthopedic condition that is associated with functional and cosmetic impairment. Results of
orthopedic procedures are usually inconsistent and cosmetic results are far from satisfactory in these patients. A silicone-gel-filled
calf prosthesis was used to correct the shoulder contour in a patient with Sprengel deformity. Cosmetically the deformity
can be restored by using a calf implant for patients in whom orthopedic procedures are not likely to yield a satisfactory
outcome. 相似文献
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