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Approximately 8% of all non-Hodgkin lymphomas are extranodal marginal zone B cell lymphomas of mucosa-associated lymphoid tissue (MALT), also known as MALT lymphomas. These arise at a wide range of different extranodal sites, with most cases affecting the stomach, the lung, the ocular adnexa and the thyroid. The small intestine is involved in a lower percentage of cases. Lymphoma growth in the early stages is associated with long-lasting chronic inflammation provoked by bacterial infections (e.g., Helicobacter pylori or Chlamydia psittaci infections) or autoimmune conditions (e.g., Sjögren’s syndrome or Hashimoto thyroiditis). While these inflammatory processes trigger lymphoma cell proliferation and/or survival, they also shape the microenvironment. Thus, activated immune cells are actively recruited to the lymphoma, resulting in either direct lymphoma cell stimulation via surface receptor interactions and/or indirect lymphoma cell stimulation via secretion of soluble factors like cytokines. In addition, chronic inflammatory conditions cause the acquisition of genetic alterations resulting in autonomous lymphoma cell growth. Recently, novel agents targeting the microenvironment have been developed and clinically tested in MALT lymphomas as well as other lymphoid malignancies. In this review, we aim to describe the composition of the microenvironment of MALT lymphoma, the interaction of activated immune cells with lymphoma cells and novel therapeutic approaches in MALT lymphomas using immunomodulatory and/or microenvironment-targeting agents.  相似文献   
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BackgroundPancreatic cancer remains a relevant clinical problem due to poor prognosis. Even after curative pancreaticoduodenectomy tumor recurrences occur in up to 80%. Risk factors for postoperative tumor recurrences have been identified before, but data on risk factors for tumor recurrences in patients with long-term-survival is scarce.MethodsIn this retrospective study consecutive long-term survival-patients (defined as at least 60 months survival) undergoing pancreaticoduodenectomy for pancreatic cancer from 2007–2014 were identified in the 2nd largest pancreatic surgery center in Germany. Clinical, pathohistological and laboratory values were analyzed to identify risk factors for tumor recurrence.ResultsThirty-four of one-hundred-sixty-seven patients were identified as long-term-survival-patients in the study period. Of those, 10 patients (29.4%) suffered from tumor recurrence. Lymph vessel invasion was identified as an independent risk factor (P=0.031, hazard ratio 13.127, 95% confidence interval: 1.270–135.698). Median postoperative time to tumor recurrence in long-term-survival-patients was 49 months. Overall survival after diagnosis of tumor recurrence was 33 months. 80% (N=8) of the patients were asymptomatic. Half of the patients (N=5) suffered from local disease, with 40% undergoing curative tumor resection. CA 19-9 levels were significantly elevated at 57 U/mL (normal <27 U/mL).ConclusionsTumor recurrence in long-term-survival-patients is typically asymptomatic. Especially long-term-survival-patients with lymph vessel invasion are more likely to develop tumor recurrence. Therefore, a structured follow-up program including CT-scans and CA 19-9 surveillance must be continued in all patients undergoing pancreaticoduodenectomy even in cases of long-term-survival.  相似文献   
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Some animals have evolved task differentiation among their eyes. A particular example is spiders, where most species have eight eyes, of which two (the principal eyes) are used for object discrimination, whereas the other three pairs (secondary eyes) detect movement. In the ctenid spider Cupiennius salei, these two eye types correspond to two visual pathways in the brain. Each eye is associated with its own first- and second-order visual neuropil. The second-order neuropils of the principal eyes are connected to the arcuate body, whereas the second-order neuropils of the secondary eyes are linked to the mushroom body. We explored the principal- and secondary eye visual pathways of the jumping spider Marpissa muscosa, in which size and visual fields of the two eye types are considerably different. We found that the connectivity of the principal eye pathway is the same as in C. salei, while there are differences in the secondary eye pathways. In M. muscosa, all secondary eyes are connected to their own first-order visual neuropils. The first-order visual neuropils of the anterior lateral and posterior lateral eyes are connected with a second-order visual neuropil each and an additional shared one (L2). In the posterior median eyes, the axons of their first-order visual neuropils project directly to the arcuate body, suggesting that the posterior median eyes do not detect movement. The L2 might function as an upstream integration center enabling faster movement decisions.  相似文献   
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Abstract

Background: The association between the Joint Committee on Infant Hearing (JCIH) risk factors and etiology of hearing loss (HL) is not studied well in children.

Objectives: To clarify the etiologic causes and evaluate the JCIH risk characteristics of children with HL.

Methods: A retrospective study of 296 children with HL born between 2009.01 and 2013.12 in Stokholm. Demographic data, family and medical histories, audiologic results, imaging findings, and genetic results were ascertained and analyzed.

Results: In 221 with bilateral hearing loss (BHL), family history and neonatal risk indicators were the most common risks (59 each), followed by syndrome related risks. In 75 with unilateral hearing loss (UHL), craniofacial anomaly was the most common risk, followed by family history. Etiology was established in 93 with BHL, in which syndromic HL accounted for 37.2%, chromosomal aberrations for 21.3%, and environmental causes for 19.1%. Etiology was established in 35 with UHL, in which ear malformation accounted for the most (74.3%), followed by environmental causes (14.3%).

Conclusions and significance: Childhood HL can be attributed to a variety of causes with an etiology identifiable in 42.5% of BHL and 46.7% of UHL. BHL and UHL have different patterns of JCIH risk exposure and etiology.  相似文献   
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Optical visualization of neural network activity is limited by imaging system‐dependent technical tradeoffs. To overcome these constraints, we have developed a powerful low‐cost and flexible imaging system with high spectral variability and unique spatio‐temporal precision for simultaneous optical recording and manipulation of neural activity of large cell groups. The system comprises eight high‐power light‐emitting diodes, a camera with a large metal‐oxide‐semiconductor sensor and a high numerical aperture water‐dipping objective. It allows fast and precise control of excitation and simultaneous low noise imaging at high resolution. Adjustable apertures generated two independent areas of variable size and position for simultaneous optical activation and image capture. The experimental applicability of this system was explored in semi‐isolated preparations of larval axolotl (Ambystoma mexicanum) with intact inner ear organs and central nervous circuits. Cyclic galvanic stimulation of semicircular canals together with glutamate‐ and γ‐aminobutyric acid (GABA)‐uncaging caused a corresponding modulation of Ca2+ transients in central vestibular neurons. These experiments revealed specific cellular properties as well as synaptic interactions between excitatory and inhibitory inputs, responsible for spatio‐temporal‐specific sensory signal processing. Location‐specific GABA‐uncaging revealed a potent inhibitory shunt of vestibular nerve afferent input in the predominating population of tonic vestibular neurons, indicating a considerable impact of local and commissural inhibitory circuits on the processing of head/body motion‐related signals. The discovery of these previously unknown properties of vestibular computations demonstrates the merits of our novel microscope system for experimental applications in the field of neurobiology.  相似文献   
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