What web-based intervention for chronic cancer-related fatigue works best for whom?:Explorative moderation analyses of a randomized controlled trial

Purpose Approximately 25% of cancer patients suffer from chronic cancer-related fatigue (CCRF), which is a complex, multifactorial condition. While there are evidence-based interventions, it remains unclear what treatment works best for the individual patient. This study explored whether baseline characteristics moderated the effect of web-based mindfulness-based cognitive therapy (eMBCT) versus ambulant activity feedback (AAF) and a psycho-education control group (PE) on fatigue in patients suffering from CCRF. Methods In a randomized controlled trial, participant suffering from CCRF participated in either eMBCT, AAF, or PE. Complete data of the treatment-adherent sample (≥ 6 sessions) was used to explore whether sociodemographic, clinical, and psychological characteristics at baseline moderated the intervention effect on fatigue severity at 6 months. Results A trend showed that baseline fatigue severity and fatigue catastrophizing moderated the intervention effect. That is, at low levels of fatigue severity and catastrophizing, patients benefited more from AAF than from eMBCT and at high levels of fatigue severity and catastrophizing, patients benefited more from eMBCT than from PE. Conclusions This study found some preliminary evidence on what treatment works best for the individual suffering from CCRF. These findings emphasize the potential gain in effectiveness of personalizing treatment. An alternative approach that might help us further in answering the question “what treatment works best for whom?” is discussed

Site-specific deletions involving the tal-1 and sil genes are restricted to cells of the T cell receptor alpha/beta lineage: T cell receptor delta gene deletion mechanism affects multiple genes

Site-specific deletions in the tal-1 gene are reported to occur in 12-26% of T cell acute lymphoblastic leukemias (T-ALL). So far two main types of tal-1 deletions have been described. Upon analysis of 134 T-ALL we have found two new types of tal-1 deletions. These four types of deletions juxtapose the 5' part of the tal-1 gene to the sil gene promoter, thereby deleting all coding sil exons but leaving the coding tal-1 exons undamaged. The recombination signal sequences (RSS) and fusion regions of the tal-1 deletion breakpoints strongly resemble the RSS and junctional regions of immunoglobulin/T cell receptor (TCR) gene rearrangements, which implies that they are probably caused by the same V(D)J recombinase complex. Analysis of the 134 T-ALL suggested that the occurrence of tal-1 deletions is associated with the CD3 phenotype, because no tal-1 deletions were found in 25 TCR-gamma/delta + T-ALL, whereas 8 of the 69 CD3- T-ALL and 11 of the 40 TCR-alpha/beta + T-ALL contained such a deletion. Careful examination of all TCR genes revealed that tal-1 deletions exclusively occurred in CD3- or CD3+ T-ALL of the alpha/beta lineage with a frequency of 18% in T-ALL with one deleted TCR-delta allele, and a frequency of 34% in T-ALL with TCR-delta gene deletions on both alleles. Therefore, we conclude that alpha/beta lineage commitment of the T-ALL and especially the extent of TCR-delta gene deletions determines the chance of a tal-1 deletion. This suggests that tal-1 deletions are mediated via the same deletion mechanism as TCR-delta gene deletions

Unexpected late-time temperature increase observed in two neutron star crust cooling sources -- XTE~J1701-462 and EXO~0748-676

Transient LMXBs that host neutron stars (NSs) provide excellent laboratories for probing the dense matter physics present in NS crusts. During accretion outbursts in LMXBs, exothermic reactions may heat the NS crust, disrupting the crust-core equilibrium. When the outburst ceases, the crust cools to restore thermal equilibrium with the core. Monitoring this evolution allows us to probe the dense matter physics in the crust. Properties of the deeper crustal layers can be probed at later times after the end of the outburst. We report on the unexpected late-time temperature evolution (>2000 days after the end of their outbursts) of two NSs in LMXBs, XTE J1701-462 and EXO 0748-676. Although both these sources exhibited very different outbursts (in terms of duration and the average accretion rate), they exhibit an unusually steep decay of ~7 eV in the observed effective temperature (occurring in a time span of ~700 days) around ~2000 days after the end of their outbursts. Furthermore, they both showed an even more unexpected rise of ~3 eV in temperature (over a time period of ~500-2000 days) after this steep decay. This rise was significant at the 2.4{\sigma} and 8.5{\sigma} level for XTE J1701-462 and EXO 0748-676, respectively. The physical explanation for such behaviour is unknown and cannot be straightforwardly be explained within the cooling hypothesis. In addition, this observed evolution cannot be well explained by low-level accretion either without invoking many assumptions. We investigate the potential pathways in the theoretical heating and cooling models that could reproduce this unusual behaviour, which so far has been observed in two crust-cooling sources. Such a temperature increase has not been observed in the other NS crust-cooling sources at similarly late times, although it cannot be excluded that this might be a result of the inadequate sampling obtained at such late times.Comment: accepted for publication by A&A letter

Basic helix-loop-helix proteins E2A and HEB induce immature T-cell receptor rearrangements in nonlymphoid cells

T-cell receptor (TCR) gene rearrangements are mediated via V(D)J recombination, which is strictly regulated during lymphoid differentiation, most probably through the action of specific transcription factors. Investigated was whether cotransfection of RAG1 and RAG2 genes in combination with lymphoid transcription factors can induce TCR gene rearrangements in nonlymphoid human cells. Transfection experiments showed that basic helix-loop-helix transcription factors E2A and HEB induce rearrangements in the TCRD locus (Ddelta2-Ddelta3 and Vdelta2-Ddelta3) and TCRG locus (psi Vgamma7-Jgamma2.3 and Vgamma8-Jgamma2.3). Analysis of these rearrangements and their circular excision products revealed some peculiar characteristics. The Vdelta2-Ddelta3 rearrangements were formed by direct coupling without intermediate Ddelta2 gene segment usage, and most Ddelta2-Ddelta3 recombinations occurred via direct coupling of the respective upstream and downstream recombination signal sequences (RSSs) with deletion of the Ddelta2 and Ddelta3 coding sequences. Subsequently, the E2A/HEB-induced TCR gene recombination patterns were compared with those in early thymocytes and acute lymphoblastic leukemias of T- and B-lineage origin, and it was found that the TCR rearrangements in the transfectants were early (immature) and not necessarily T-lineage specific. Apparently, some parts

Lymph node removal enhances corneal graft survival in mice at high risk of rejection

Peer reviewedPublisher PD

What web-based intervention for chronic cancer-related fatigue works best for whom? Explorative moderation analyses of a randomized controlled trial

PURPOSE: Approximately 25% of cancer patients suffer from chronic cancer-related fatigue (CCRF), which is a complex, multifactorial condition. While there are evidence-based interventions, it remains unclear what treatment works best for the individual patient. This study explored whether baseline characteristics moderated the effect of web-based mindfulness-based cognitive therapy (eMBCT) versus ambulant activity feedback (AAF) and a psycho-education control group (PE) on fatigue in patients suffering from CCRF. METHODS: In a randomized controlled trial, participant suffering from CCRF participated in either eMBCT, AAF, or PE. Complete data of the treatment-adherent sample (≥ 6 sessions) was used to explore whether sociodemographic, clinical, and psychological characteristics at baseline moderated the intervention effect on fatigue severity at 6 months. RESULTS: A trend showed that baseline fatigue severity and fatigue catastrophizing moderated the intervention effect. That is, at low levels of fatigue severity and catastrophizing, patients benefited more from AAF than from eMBCT and at high levels of fatigue severity and catastrophizing, patients benefited more from eMBCT than from PE. CONCLUSIONS: This study found some preliminary evidence on what treatment works best for the individual suffering from CCRF. These findings emphasize the potential gain in effectiveness of personalizing treatment. An alternative approach that might help us further in answering the question “what treatment works best for whom?” is discussed