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Treatment of lymphoma can be associated with cognitive challenges, and some patients may fear development of dementia as long-term complication. Studies report a lower risk of dementia after cancer. Some believe this difference to be a protective mechanism of cancer, others believe it to be driven by bias. The risk of developing dementia after lymphoma has not been investigated in a population-based setting. The aim of this study was to identify the risk of being diagnosed with dementia after lymphoma treatment. This Danish nationwide matched cohort study included patients aged ≥65 years with a first-time diagnosis of a non-central nervous system lymphoma between 2005 and 2018 in complete remission after treatment with chemotherapy. Patients diagnosed with dementia or treated with dementia medication before lymphoma diagnosis were excluded. Each patient was matched 1:5 on sex, year of birth, and a modified Charlson comorbidity index. Patients and matched comparators were followed from the corresponding patient's date of complete remission. The risk of developing dementia was calculated using cause-specific hazard ratios (HR), and the cumulative risk was estimated by Aalen-Johansen with death as the competing risk. A total of 3,244 patients and 16,220 matched comparators were included in the study. There was no difference in risk of all-cause dementia among patients with lymphoma compared to matched comparators with cause-specific HR of 0.85 (95% confidence interval [CI]: 0.70;1.04). The risk of both Alzheimer's disease and non-Alzheimer's dementia was equal among patients and comparators: HR 0.89 (95% CI: 0.66;1.21) and 0.82 (95% CI: 0.63;1.07), respectively. Stratified by lymphoma subtype, age, or year of diagnosis, the risk of all-cause dementia remained equal among patients and matched comparators. The cumulative risk of all-cause dementia was significantly lower among patients with lymphoma compared to matched comparators (Gray's test p < 0.001), probably reflecting higher mortality in patients with lymphoma. The risk of all-cause dementia, Alzheimer's disease, and non-Alzheimer's dementia was equal among older patients with lymphoma compared to matched comparators. Our data suggests that risk of developing dementia is not changed after lymphoma treatment. [ABSTRACT FROM AUTHOR]

Background Hazelnut allergy is birch pollen–driven in Northern/Western Europe and lipid transfer protein–driven in Spain and Italy. Little is known about other regions and other allergens. Objective Establishing a molecular map of hazelnut allergy across Europe. Methods In 12 European cities, subjects reporting reactions to hazelnut (n = 731) were evaluated and sensitization to 24 foods, 12 respiratory allergen sources, and latex was tested by using skin prick test and ImmunoCAP. A subset (124 of 731) underwent a double-blind placebo-controlled food challenge to hazelnut. Sera of 423 of 731 subjects were analyzed for IgE against 7 hazelnut allergens and cross-reactive carbohydrate determinants by ImmunoCAP. Results Hazelnut allergy was confirmed in 70% of those undergoing double-blind placebo-controlled food challenges. Birch pollen–driven hazelnut sensitization (Cor a 1) dominated in most cities, except in Reykjavik, Sofia, Athens, and Madrid, where reporting of hazelnut allergy was less frequent anyhow. In Athens, IgE against Cor a 8 dominated and strongly correlated with IgE against walnut, peach, and apple and against Chenopodium , plane tree, and mugwort pollen. Sensitization to seed storage proteins was observed in less than 10%, mainly in children, and correlated with IgE to nuts, seeds, and legumes. IgE to Cor a 12, observed in all cities (10% to 25%), correlated with IgE to nuts, seeds, and pollen. Conclusions In adulthood, the importance of hazelnut sensitization to storage proteins, oleosin (Cor a 12), and Cor a 8 is diluted by the increased role of birch pollen cross-reactivity with Cor a 1. Cor a 8 sensitization in the Mediterranean is probably driven by diet in combination with pollen exposure. Hazelnut oleosin sensitization is prevalent across Europe; however, the clinical relevance remains to be established. [ABSTRACT FROM AUTHOR]

Background Precautionary labeling is used to warn consumers of the presence of unintended allergens, but the lack of agreed allergen thresholds can result in confusion and risk taking by patients with food allergy. The lack of data on threshold doses below which subjects are unlikely to react is preventing the development of evidence-based allergen management strategies that are understood by clinician and patient alike. Objective We sought to define threshold dose distributions for 5 major allergenic foods in the European population. Methods Patients with food allergy were drawn from the EuroPrevall birth cohort, community surveys, and outpatient clinic studies and invited to undergo a food challenge. Low-dose, double-blind, placebo-controlled food challenges were undertaken with commercially available food ingredients (peanut, hazelnut, celery, fish, and shrimp) blinded into common matrices. Dose distributions were modeled by using interval-censoring survival analysis with 3 parametric approaches. Results Of the 5 foods used for challenge, 4 produced similar dose distributions, with estimated doses eliciting reactions in 10% of the allergic population (ED 10 ), ranging from 1.6 to 10.1 mg of protein for hazelnut, peanut, and celery with overlapping 95% CIs. ED 10 values for fish were somewhat higher (27.3 mg of protein), although the CIs were wide and overlapping between fish and plant foods. Shrimp provided radically different dose distributions, with an ED 10 value of 2.5 g of protein. Conclusion This evidence base will contribute to the development of reference doses and action levels for allergens in foods below which only the most sensitive subjects might react. [ABSTRACT FROM AUTHOR]

Background: Kiwifruit is a common cause of food allergy. Symptoms range from mild to anaphylactic reactions. Objective: We sought to elucidate geographic differences across Europe regarding clinical patterns and sensitization to kiwifruit allergens. Factors associated with the severity of kiwifruit allergy were identified, and the diagnostic performance of specific kiwifruit allergens was investigated. Methods: This study was part of EuroPrevall, a multicenter European study investigating several aspects of food allergy. Three hundred eleven patients with kiwifruit allergy from 12 countries representing 4 climatic regions were included. Specific IgE to 6 allergens (Act d 1, Act d 2, Act d 5, Act d 8, Act d 9, and Act d 10) and kiwifruit extract were tested by using ImmunoCAP. Results: Patients from Iceland were mainly sensitized to Act d 1 (32%), those from western/central and eastern Europe were mainly sensitized to Act d 8 (pathogenesis-related class 10 protein, 58% and 44%, respectively), and those from southern Europe were mainly sensitized to Act d 9 (profilin, 31%) and Act d 10 (nonspecific lipid transfer protein, 22%). Sensitization to Act d 1 and living in Iceland were independently and significantly associated with severe kiwifruit allergy (odds ratio, 3.98 [P = .003] and 5.60 [P < .001], respectively). Using a panel of 6 kiwifruit allergens in ImmunoCAP increased the diagnostic sensitivity to 65% compared with 20% for skin prick tests and 46% ImmunoCAP using kiwi extract. Conclusion: Kiwifruit allergen sensitization patterns differ across Europe. The use of specific kiwifruit allergens improved the diagnostic performance compared with kiwifruit extract. Sensitization to Act d 1 and living in Iceland are strong risk factors for severe kiwifruit allergy. [ABSTRACT FROM AUTHOR]

Abstract: Let denote the symmetric group on and the stabilizer subgroup of . We derive algorithms for computing Fourier transforms of left and right -invariant signals that require a total of additions and scalar multiplications. Furthermore we show that the convolution of such signals can also be computed in time linear in . [Copyright &y& Elsevier]

Abstract: By definition, a P2-graph is an undirected graph in which every vertex is contained in a path of length two. For such a graph, denotes the minimum number of paths of length two that cover all vertices of . We prove that and show that these upper and lower bounds are tight. Furthermore we show that every connected P2-graph contains a spanning tree such that . We present a linear time algorithm that produces optimal 2-path covers for trees. This is contrasted by the result that the decision problem is -complete for trivalent graphs. This graph theoretical problem originates from the task of searching a large database of biological molecules such as the Protein Data Bank (PDB) by content. [Copyright &y& Elsevier]

Background: The association between allergic sensitization and eczema has been debated for years. Objective: We sought to determine and compare the strength of the association between allergen skin sensitization and eczema in both developing and industrialized countries. Methods: Twenty-eight thousand five hundred ninety-one randomly selected 8- to 12-year-old schoolchildren in 20 countries were physically examined for flexural eczema and received skin prick testing to Dermatophagoides pteronyssinus, Dermatophagoides farinae, cat hair, Alternaria tenuis, mixed tree and grass pollen, and allergens of local relevance. Results: The age- and sex-adjusted odds ratios (ORs) for a positive association between flexural eczema and atopy ranged between 0.74 (95% CI, 0.31-1.81) and 4.53 (95% CI, 1.72-11.93), with a significantly stronger association in affluent compared with nonaffluent countries (combined age- and sex-adjusted ORaffluent = 2.69 [95% CI, 2.31-3.13] and ORnonaffluent = 1.17 [95% CI, 0.81-1.70]). The combined population attributable fraction for atopy in flexural eczema was 27.9% for affluent and 1.2% for nonaffluent-country centers. Correlating gross national per-capita income with either ORs or population attributable fractions for atopy in flexural eczema confirmed a highly significant positive association (P = .006 and P < .001, respectively). Conclusions: The association between atopy and flexural eczema is weak and more variable than previously suggested, and the strength of this association is positively linked to gross national income. [Copyright &y& Elsevier]

Background Optimal treatment strategy for the oldest patients with diffuse large B-cell lymphoma (DLBCL) remains controversial, as this group often is precluded from clinical trials, and population-based studies are limited. Methods All Danish DLBCL-patients ≥75 years diagnosed from 2003 to 2012 were identified, using the Danish National Lymphoma Registry (LYFO). Information regarding baseline characteristics, treatment, comorbidities and outcomes was retrieved from LYFO, the Danish National health registries and medical records. Patients were stratified by age (75–79; 80–84 and 85 + years), comorbidity score and treatment modality (standard treatment [R-CHOP/CHOP-like], less intensive regimens or palliative treatment). Findings A total of 1011 patients were included. Standard treatment was initiated in 64%, ranging from 83% among patients aged 75–79 years to 32% among patient aged 85 + years. With standard treatment, median overall survival (OS) estimates were 4·6, 2·6, and 1·9 years for the age groups 75–79, 80–84 and 85+ years. Among patient aged 75–79 and 80–84 years, OS was superior with standard treatment, although high comorbidity scores attenuated this association. Among patients aged 85+ years, survival was not influenced by treatment intensity. Patients ≥80 years had similar OS regardless of intended (R-)CHOP dosing, whereas patients of 75–79 years scheduled for full dose had higher OS. Standard treatment was not associated with increased hospitalisation. Interpretation Standard treatment is feasible with good outcomes in a large proportion of elderly DLBCL-patients. Planned dose reduction in patients aged ≥80 years had no negative impact on OS. [ABSTRACT FROM AUTHOR]

Summary The mechanosensitive two-pore domain (K2P) K + channels (TREK-1, TREK-2, and TRAAK) are important for mechanical and thermal nociception. However, the mechanisms underlying their gating by membrane stretch remain controversial. Here we use molecular dynamics simulations to examine their behavior in a lipid bilayer. We show that TREK-2 moves from the “down” to “up” conformation in direct response to membrane stretch, and examine the role of the transmembrane pressure profile in this process. Furthermore, we show how state-dependent interactions with lipids affect the movement of TREK-2, and how stretch influences both the inner pore and selectivity filter. Finally, we present functional studies that demonstrate why direct pore block by lipid tails does not represent the principal mechanism of mechanogating. Overall, this study provides a dynamic structural insight into K2P channel mechanosensitivity and illustrates how the structure of a eukaryotic mechanosensitive ion channel responds to changes in forces within the bilayer. [ABSTRACT FROM AUTHOR]

Purpose Development of secondary central nervous system involvement (SCNS) in patients with diffuse large B-cell lymphoma is associated with poor outcomes. The CNS International Prognostic Index (CNS-IPI) has been proposed for identifying patients at greatest risk, but the optimal model is unknown. Methods We retrospectively analysed patients with diffuse large B-cell lymphoma diagnosed between 2001 and 2013, staged with PET/CT and treated with R-CHOP(-like) regimens. Baseline clinicopathologic characteristics, treatments, and outcome data were collected from clinical databases and medical files. We evaluated the association between candidate prognostic factors and modelled different risk models for predicting SCNS. Results Of 1532 patients, 62 (4%) subsequently developed SCNS. By multivariate analysis, disease stage III/IV, elevated serum LDH, kidney/adrenal and uterine/testicular involvement were independently associated with SCNS. There was a strong correlation between absolute number of extranodal sites and risk of SCNS; the 144 patients (9%) with >2 extranodal sites had a 3-year cumulative incidence of SCNS of 15.2% (95% confidence interval [CI] 9.2–21.2%) compared with 2.6% (95% CI 1.7–3.5) among those with ≤2 sites ( P < 0.001). The 3-year cumulative risks of SCNS for CNS-IPI defined risk groups were 11.2%, 3.1% and 0.4% for high-, intermediate- and low-risk patients, respectively. All risk models analysed had high negative predictive values, but only modest positive predictive values. Conclusions Patients with >2 extranodal sites or high-risk disease according to the CNS-IPI should be considered for baseline CNS staging. Clinical risk prediction models suffer from limited positive predictive ability, highlighting the need for more sensitive biomarkers to identify patients at highest risk of this devastating complication. [ABSTRACT FROM AUTHOR]