Follicular lymphoma in situ (FLIS) was first described nearly a decade ago, but its clinical significance remains uncertain. We reevaluated our original series and more recently diagnosed cases to ...develop criteria for the distinction of FLIS from partial involvement by follicular lymphoma (PFL). A total of 34 cases of FLIS were identified, most often as an incidental finding in a reactive lymph node. Six of 34 patients had prior or concurrent FL, and 5 of 34 had FLIS composite with another lymphoma. Of patients with negative staging at diagnosis and available follow-up (21 patients), only one (5%) developed FL (follow-up: median, 41 months; range, 10-118 months). Follow-up was not available in 2 cases. Fluorescence in situ hybridization for BCL2 gene rearrangement was positive in all 17 cases tested. PFL patients were more likely to develop FL, diagnosed in 9 of 17 (53%) who were untreated. Six patients with PFL were treated with local radiation therapy (4) or rituximab (2) and remained with no evidence of disease. FLIS can be reliably distinguished from PFL and has a very low rate of progression to clinically significant FL. FLIS may represent the tissue counterpart of circulating t(14;18)-positive B cells.
A disruption of sebocyte differentiation and lipogenesis has fatal consequences and can cause a wide spectrum of skin diseases, from acne vulgaris to sebaceous carcinoma, however, the relevant ...molecular mechanisms have not been fully clarified.
The induction of autophagy and apoptosis in human sebocytes in response to biologically relevant fatty acids was investigated.
Free fatty acids (arachidonic acid, linoleic acid, palmitic acid, and palmitoleic acid) and the pan-caspase inhibitor QVD-Oph were added to the supernatant of cultured human SZ95 sebocytes. Individual relevant proteins were analyzed by Western blotting. Apoptosis and cell viability were determined, and typical autophagy structures were detected through electron microscopy. To obtain cell growth curves, cell confluence was continuously monitored by real-time cell analysis.
Fatty acids induced the development of intracellular lipid droplets with subsequent apoptosis, whereas arachidonic acid caused the most rapid effect. Cleavage products of caspase-3 were only detected in arachidonic acid-induced apoptosis. The high basal apoptotic rate of cultured SZ95 sebocytes was strongly suppressed by QVD-Oph. Fatty acid-induced apoptosis was also markedly inhibited by QVD-Oph, whereas intracellular lipid droplets further accumulated. While cell viability after incubation with linoleic acid, palmitic acid, or palmitoleic acid and QVD-Oph was comparable with that of non-treated controls, arachidonic acid significantly reduced cell viability and cell density despite the concomitant pan-caspase inhibitor treatment. Using electron microscopy, typical autophagy structures were detected, such as autophagosomes and autolysosomes, at the basal level, which became more pronounced after treatment with fatty acids.
Our findings contribute to a better understanding of the inflammation-associated mechanisms of lipogenesis and cell death induction in human sebocytes and may help to unveil the effects of fatty acid-rich human nutrition.
Expansion of a single repetitive DNA sequence, termed a tandem repeat (TR), is known to cause more than 50 diseases
. However, repeat expansions are often not explored beyond neurological and ...neurodegenerative disorders. In some cancers, mutations accumulate in short tracts of TRs, a phenomenon termed microsatellite instability; however, larger repeat expansions have not been systematically analysed in cancer
. Here we identified TR expansions in 2,622 cancer genomes spanning 29 cancer types. In seven cancer types, we found 160 recurrent repeat expansions (rREs), most of which (155/160) were subtype specific. We found that rREs were non-uniformly distributed in the genome with enrichment near candidate cis-regulatory elements, suggesting a potential role in gene regulation. One rRE, a GAAA-repeat expansion, located near a regulatory element in the first intron of UGT2B7 was detected in 34% of renal cell carcinoma samples and was validated by long-read DNA sequencing. Moreover, in preliminary experiments, treating cells that harbour this rRE with a GAAA-targeting molecule led to a dose-dependent decrease in cell proliferation. Overall, our results suggest that rREs may be an important but unexplored source of genetic variation in human cancer, and we provide a comprehensive catalogue for further study.
This retrospective study was performed to evaluate the efficacy of three‐dimensional (3D)‐navigated multiprobe radiofrequency ablation (RFA) with intraprocedural image fusion for treatment of ...hepatocellular carcinoma (HCC) by histopathological examination. From 2009 to 2018, 97 patients (84 men, 13 women; median age, 60 years; range, 1‐71) were transplanted after bridging therapy of 195 HCCs by stereotactic RFA (SRFA). The median interval between the first SRFA and transplantation was 6.8 months (range, 0‐71). The rate of residual vital tissue (RVT) could be assessed in 188 of 195 lesions in 96 of 97 patients by histological examination of the explanted livers using hematoxylin and eosin (H&E) and Tdt‐mediated UTP nick‐end labeling (TUNEL) stains. Histopathological results were compared with the findings of the last computed tomography (CT) imaging before liver transplantation (LT). Median number and size of treated tumors were 1 (range, 1‐8) and 2.5 cm (range, 1‐8). Complete radiological response was achieved in 186 of 188 nodules (98.9%) and 94 of 96 patients (97.9%) and complete pathological response in the explanted liver specimen in 183 of 188 nodules (97.3%) and 91 of 96 patients (94.8%), respectively. In lesions ≥3 cm, complete tumor cell death was achieved in 50 of 52 nodules (96.2%). Residual tumor did not correlate with tumor size (P = 0.5). Conclusion: Multiprobe SRFA with intraprocedural image fusion represents an efficient, minimally invasive therapy for HCC, even with tumor sizes larger than 3 cm, and without the need of a combination with additional treatments. The results seem to justify the additional efforts related to the stereotactic approach.
Networked operation of unmanned air vehicles (UAVs) demands fusion of information from disparate sources for accurate flight control. In this investigation, a novel sensor fusion architecture for ...detecting aircraft runway and horizons as well as enhancing the awareness of surrounding terrain is introduced based on fusion of enhanced vision system (EVS) and synthetic vision system (SVS) images. EVS and SVS image fusion has yet to be implemented in real-world situations due to signal misalignment. We address this through a registration step to align EVS and SVS images. Four fusion rules combining discrete wavelet transform (DWT) sub-bands are formulated, implemented, and evaluated. The resulting procedure is tested on real EVS-SVS image pairs and pairs containing simulated turbulence. Evaluations reveal that runways and horizons can be detected accurately even in poor visibility. Furthermore, it is demonstrated that different aspects of EVS and SVS images can be emphasized by using different DWT fusion rules. The procedure is autonomous throughout landing, irrespective of weather. The fusion architecture developed in this study holds promise for incorporation into manned heads-up displays (HUDs) and UAV remote displays to assist pilots landing aircraft in poor lighting and varying weather. The algorithm also provides a basis for rule selection in other signal fusion applications.
Emotion dysregulation (ED) is a key target for change among empirically supported treatments for emotional disorders, including dialectical behaviour therapy skills training (DBT‐ST), yet how ...treatments improve ED is poorly understood. Using data from a randomised trial of DBT‐ST versus supportive group therapy for transdiagnostic ED, we tested whether three mechanistic variables—behavioural skills use, mindfulness, and perceived control—explain variability in ED within people over time. We additionally explored the mediating roles of these variables between conditions. Adults with transdiagnostic ED (N = 44) participated in weekly groups for 4 months, with assessments at pre‐, mid‐ and post‐treatment and at 2‐month follow‐up. As hypothesised, multilevel models disaggregating within‐ and between‐person effects indicated that skills use, mindfulness, and perceived control each had significant total and unique within‐person associations with ED at concurrent time points, net the effect of time. Unexpectedly, these within‐person relations were not significant for mechanistic variables predicting ED 2 months later. Further, unique between‐person variability in skills use, mindfulness, and perceived control did not significantly mediate the relationship between condition and ED improvements. The present study is an important step in clarifying ED mechanisms of change, both within and between persons.
This qualitative study aimed to understand how early adopting health care organizations (HCOs) implement the documentation of patients' disability status and accommodation needs in the electronic ...health record (EHR).
The authors conducted qualitative interviews with HCOs that had active or past initiatives to implement systematic collection of disability status in the EHR. The interviews elicited participants' current experiences, desired features of a standard EHR build, and challenges and successes. A team-based analysis approach was used to review and summarize quotations to identify themes and categorize text that exemplified identified themes.
Themes identified from the interviews included "why" organizations collected disability status; of "what" their EHR build consisted, including who collected, how often data were collected, and what data were collected; and "how" organizations were implementing systematic collection. The main purpose for collection of disability status and accommodation needs was to prepare for patients with disabilities. Due to this priority, participants believed collection should (1) occur prior to patients' clinical encounters, (2) be conducted regularly, (3) use standardized language, and (4) be available in a highly visible location in the EHR. Leadership support to integrate collection into existing workflows was essential for success.
Patients with disabilities experience significant disparities in the receipt of equitable health care services. To provide equitable care, HCOs need to systematically collect disability status and accommodation needs in the EHR to ensure that they are prepared to provide equitable care to all patients with disabilities.
Supramolecular self-assembly at the solid–solid interface enables the deposition and monolayer formation of insoluble organic semiconductors under ambient conditions. The underlying process, termed ...as the organic solid–solid wetting deposition (OSWD), generates two-dimensional adsorbates directly from dispersed three-dimensional organic crystals. This straightforward process has important implications in various fields of research and technology, such as in the domains of low-dimensional crystal engineering, the chemical doping and band gap engineering of graphene, and in the area of field-effect transistor fabrication. However, to date, lack of an in-depth understanding of the physicochemical basis of the OSWD prevented the identification of important parameters, essential to achieve a better control of the growth of monolayers and supramolecular assemblies with defined structures, sizes, and coverage areas. Here we propose a detailed model for the OSWD, derived from experimental and theoretical results that have been acquired by using the organic semiconductor quinacridone as an example system. The model reveals the vital role of the ζ potential and includes Casimir-like fluctuation-induced forces and the effect of dewetting in hydrophobic nanoconfinements. Based on our results, the OSWD of insoluble organic molecules can hence be applied to environmental friendly and low-cost dispersing agents, such as water. In addition, the model substantially enhances the ability to control the OSWD in terms of adsorbate structure and substrate coverage.
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