Enteropathy-associated T-cell lymphoma (EATL), an uncommon lymphoma of intestinal intraepithelial T lymphocytes, occurs with a higher frequency in northern Europe due to association with celiac ...disease. Data on the occurrence of EATL in the Asian population, among whom celiac disease is very rare, are conflicting. This study aimed to characterize EATL encountered in the Chinese population in Hong Kong. Eighteen cases were identified, all fulfilling the criteria of type II rather than classical EATL. The patients, including 13 men and 5 women, had a median age of 62 years. Most presented with small bowel perforation, and there was no history of malabsorption. The clinical course was aggressive, with 14 of 16 patients dying of progressive disease or complications, usually within 1 year. The histologic features were practically identical in all cases. The central zone of the tumor showed ulceration with or without perforation and was characterized by monotonous transmural infiltration of the bowel by small-sized or medium-sized lymphoma cells with few admixed inflammatory cells and no coagulative necrosis. The peripheral zone featured lateral spread of lymphoma cells in the mucosa, accompanied by variable involvement of the submucosa and muscularis. In all cases, there was an intraepithelial lymphocytosis zone contiguous or discontinuous with the peripheral zone, which was characterized by infiltration of the intestinal epithelium by nonatypical small lymphocytes, and not accompanied by other histologic changes of enteropathy. The most common phenotype of the lymphoma cells was CD3+, CD5-, CD4-, CD8+, CD56+, TIA1+, CD30-, and Epstein-Barr virus, and 2 cases showed aberrant expression of CD20. A remarkable finding was that 14 (78%) cases expressed γδ T-cell receptor, and only 6 (33%) expressed αβ T-cell receptor (with 3 cases coexpressing both T-cell receptors and 1 case expressing neither). The immunophenotype of the intraepithelial lymphocytes was either discordant (particularly with respect to CD8 and CD56 expressions) or concordant with the lymphoma cells of the corresponding cases. Thus, this study shows that EATL occurring in the Chinese population is exclusively of type II. In contrast to several studies, intraepithelial lymphocytosis can be consistently demonstrated and this component seems to represent a precursor lesion of EATL rather than a manifestation of celiac disease. In view of the differences in epidemiology and clinicopathologic features, we believe it is justified to separate out type II EATL from the EATL category as a distinct form of lymphoma, for which we propose the designation "monomorphic intestinal T-cell lymphoma."
How do state and protester violence affect whether protests grow or shrink? Previous research finds conflicting results for how violence affects protest dynamics. This article argues that ...expectations and emotions should generate an n-shaped relationship between the severity of state repression and changes in protest size the next day. Protester violence should reduce the appeal of protesting and increase the expected cost of protesting, decreasing subsequent protest size. Since testing this argument requires precise measurements, a pipeline is built that applies convolutional neural networks to images shared in geolocated tweets. Continuously valued estimates of state and protester violence are generated per city-day for 24 cities across five countries, as are estimates of protest size and the age and gender of protesters. The results suggest a solution to the repression-dissent puzzle and join a growing body of research benefiting from the use of social media to understand subnational conflict.
IgG4-related sclerosing disease is a recently recognized inflammatory lesion frequently involving pancreas, submandibular gland, lacrimal gland, and lymph node. We report 3 cases of ocular adnexal ...lymphoma arising in IgG4-related chronic sclerosing dacryoadenitis, a phenomenon that has not been previously reported. The patients presented with bilateral or unilateral ocular adnexal mass usually present for many years. One patient also had asymptomatic diffuse lymphadenopathy. Two patients had biopsy-proven IgG4-related chronic sclerosing dacryoadenitis before the current presentation, and 1 had systemic involvement by IgG4-related sclerosing disease as evidenced by increased IgG4+ cells in a prior nasopharyngeal biopsy. Two cases showed features of extranodal marginal zone lymphoma of mucosa-associated lymphoid-tissue type (1 with large cell transformation) and 1 follicular lymphoma. Thus, the lymphoid hyperplasia of IgG4-related sclerosing disease can provide a substrate for the emergence of lymphoma. In addition, we report 3 cases of ocular adnexal extranodal marginal zone B-cell lymphoma that show sclerosing inflammation in the background and numerous IgG4+ monotypic plasma cells. In the absence of prior biopsies or information on serum IgG4 titer, it is unclear whether these cases represent lymphoma complicating IgG4-related sclerosing disease or de novo lymphoma. Nonetheless, these cases are distinctive in that the neoplastic cells express IgG4 (light chain restricted), whereas unselected cases of ocular adnexal lymphomas do not show IgG4 expression.
Immunoglobulin G (IgG)4-related sclerosing disease is a recently described syndrome characterized by mass-forming lesions in various organs due to dense lymphoplasmacytic infiltrates and stromal ...sclerosis, elevated serum IgG4 titer, increased tissue IgG4 plasma cells, and favorable clinical outcome. We describe 4 patients with IgG4-related sclerosing mastitis, which represents a new member of this family of diseases. All patients were female with a mean age of 47.5 years, presenting with painless masses in 1 or both breasts. One patient had concurrent IgG4-related lymphadenopathy, and another had eyelid swelling of undetermined cause. The serum IgG4 titer was elevated in 1 tested patient, and circulating autoantibodies were found in 3 tested patients. All patients were well with no recurrence after excision or biopsy of the mass. Histologically, the breast masses featured dense lymphoplasmacytic infiltrates, prominent stromal sclerosis and loss of breast lobules. Phlebitis was present in 1 case. IgG4 cells ranged from 272 to 495 per high-power field, constituting 49% to 85% of all IgG cells. IgG4 cells were scarce in 9 of 9 cases of lymphocytic mastitis and 6 of 7 cases of granulomatous mastitis studied as controls. In summary, IgG4-related sclerosing mastitis appears to be a distinctive form of mastitis, sometimes accompanied by other components of IgG4-related sclerosing disease, and shows a favorable clinical outcome.
•We have characterized human mesenchymal stem cell lines from multiple donors.•Variation in key cell characteristics despite conformity to ISCT minimum criteria.•Relative difference in ...immunosuppressive potential is likely to affect clinical utility.•Differences in cell growth potential will impact on autologous process development.•The control of process parameters will be an important step in driving process consistency.
Cell-based therapies have the potential to contribute to global healthcare, whereby the use of living cells and tissues can be used as medicinal therapies. Despite this potential, many challenges remain before the full value of this emerging field can be realized. The characterization of input material for cell-based therapy bioprocesses from multiple donors is necessary to identify and understand the potential implications of input variation on process development. In this work, we have characterized bone marrow derived human mesenchymal stem cells (BM-hMSCs) from multiple donors and discussed the implications of the measurable input variation on the development of autologous and allogeneic cell-based therapy manufacturing processes. The range of cumulative population doublings across the five BM-hMSC lines over 30 days of culture was 5.93, with an 18.2% range in colony forming efficiency at the end of the culture process and a 55.1% difference in the production of interleukin-6 between these cell lines. It has been demonstrated that this variation results in a range in the process time between these donor hMSC lines for a hypothetical product of over 13 days, creating potential batch timing issues when manufacturing products from multiple patients. All BM-hMSC donor lines demonstrated conformity to the ISCT criteria but showed a difference in cell morphology. Metabolite analysis showed that hMSCs from the different donors have a range in glucose consumption of 26.98pmolcell−1day−1, Lactate production of 29.45pmolcell−1day−1 and ammonium production of 1.35pmolcell−1day−1, demonstrating the extent of donor variability throughout the expansion process. Measuring informative product attributes during process development will facilitate progress towards consistent manufacturing processes, a critical step in the translation cell-based therapies.
The organization and localization of lexico-semantic information in the brain has been debated for many years. Specifically, lesion and imaging studies have attempted to map the brain areas ...representing living versus nonliving objects, however, results remain variable. This may be due, in part, to the fact that the univariate statistical mapping analyses used to detect these brain areas are typically insensitive to subtle, but widespread, effects. Decoding techniques, on the other hand, allow for a powerful multivariate analysis of multichannel neural data. In this study, we utilize machine-learning algorithms to first demonstrate that semantic category, as well as individual words, can be decoded from EEG and MEG recordings of subjects performing a language task. Mean accuracies of 76% (chance=50%) and 83% (chance=20%) were obtained for the decoding of living vs. nonliving category or individual words respectively. Furthermore, we utilize this decoding analysis to demonstrate that the representations of words and semantic category are highly distributed both spatially and temporally. In particular, bilateral anterior temporal, bilateral inferior frontal, and left inferior temporal-occipital sensors are most important for discrimination. Successful intersubject and intermodality decoding shows that semantic representations between stimulus modalities and individuals are reasonably consistent. These results suggest that both word and category-specific information are present in extracranially recorded neural activity and that these representations may be more distributed, both spatially and temporally, than previous studies suggest.
► Support vector machines can robustly decode semantic information from EEG and MEG. ► Multivariate decoding techniques allow for detection of subtle, but distributed, effects. ► Semantic categories and individual words have distributed spatiotemporal representations. ► Representations are consistent between subjects and stimulus modalities. ► A scalable hierarchical tree decoder further improves decoding performance.
Diffuse large B-cell lymphoma that develops in the setting of long-standing chronic inflammation is typically associated with Epstein-Barr virus, and usually presents as tumor mass involving body ...cavities, as in pyothorax-associated lymphoma. It is listed as a distinct entity in the latest World Health Organization lymphoma classification. We report four cases that were incidentally discovered on histologic examination, one each in a splenic false cyst, a long-standing hydrocele, an atrial myxoma, and metallic-implant wear debris. Microscopic foci of atypical (neoplastic) large lymphoid cells were found within the contents of the cysts or curettage material, or within the stroma of the atrial myxoma. Despite the diverse clinical scenarios, all cases showed a homogeneous phenotype: positivity for B-lineage markers (CD20+, CD79a+, PAX5+), non-germinal center immunophenotype (CD10-, BCL6-/+, MUM-1+), and positivity for Epstein-Barr virus with type III latency (LMP1+, EBNA2+). The last feature supports the hypothesis that the lymphoma has arisen in a setting of 'local immunodeficiency' as a result of long-standing chronic inflammation in an enclosed space, a characteristic pathogenetic mechanism of diffuse large B-cell lymphoma associated with chronic inflammation. These cases therefore expand the spectrum of this entity to include new clinical scenarios for the development of this lymphoma type.
In Drosophila, ∼50 classes of olfactory receptor neurons (ORNs) send axons to 50 corresponding glomeruli in the antennal lobe. Uniglomerular projection neurons (PNs) relay olfactory information to ...the mushroom body (MB) and lateral horn (LH). Here, we combine single-cell labeling and image registration to create high-resolution, quantitative maps of the MB and LH for 35 input PN channels and several groups of LH neurons. We find (1) PN inputs to the MB are stereotyped as previously shown for the LH; (2) PN partners of ORNs from different sensillar groups are clustered in the LH; (3) fruit odors are represented mostly in the posterior-dorsal LH, whereas candidate pheromone-responsive PNs project to the anterior-ventral LH; (4) dendrites of single LH neurons each overlap with specific subsets of PN axons. Our results suggest that the LH is organized according to biological values of olfactory input.
In addition to its widespread clinical use, the intracranial electroencephalogram (iEEG) is increasingly being employed as a tool to map the neural correlates of normal cognitive function as well as ...for developing neuroprosthetics. Despite recent advances, and unlike other established brain-mapping modalities (e.g. functional MRI, magneto- and electroencephalography), registering the iEEG with respect to neuroanatomy in individuals—and coregistering functional results across subjects—remains a significant challenge. Here we describe a method which coregisters high-resolution preoperative MRI with postoperative computerized tomography (CT) for the purpose of individualized functional mapping of both normal and pathological (e.g., interictal discharges and seizures) brain activity. Our method accurately (within 3mm, on average) localizes electrodes with respect to an individual's neuroanatomy. Furthermore, we outline a principled procedure for either volumetric or surface-based group analyses. We demonstrate our method in five patients with medically-intractable epilepsy undergoing invasive monitoring of the seizure focus prior to its surgical removal. The straight-forward application of this procedure to all types of intracranial electrodes, robustness to deformations in both skull and brain, and the ability to compare electrode locations across groups of patients makes this procedure an important tool for basic scientists as well as clinicians.
► We describe a method for localizing intracranial electrodes in individuals. ► Post-implant CT was coregistered with pre-implant MRI. ► An optimization algorithm accounted for the brain shift caused by implantation. ► Surface-based methods were used to coregister electrode arrays across patients.
Conventional microbiological water monitoring uses culture-dependent techniques to screen indicator microbial species such as Escherichia coli and fecal coliforms. With high-throughput, ...second-generation sequencing technologies becoming less expensive, water quality monitoring programs can now leverage the massively parallel nature of second-generation sequencing technologies for batch sample processing to simultaneously obtain compositional and functional information of culturable and as yet uncultured microbial organisms. This review provides an introduction to the technical capabilities and considerations necessary for the use of second-generation sequencing technologies, specifically 16S rDNA amplicon and whole-metagenome sequencing, to investigate the composition and functional potential of microbiomes found in water and wastewater systems.
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