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Immune escape describes a critical event whereby tumor cells adopt an immunoresistant phenotype to escape adaptive surveillance. We show that expression of a pivotal negative regulator of T-cell function, B7-H1, correlates with PI(3) kinase activation in breast and prostate cancer patients. B7-H1-mediated immunoresistance can be attenuated by inhibitors of the PI(3) kinase pathway, and is dependent on S6K1-mediated translational regulation of B7-H1 protein. Breast and prostate carcinoma cells with activated PI(3) kinase lose the immunoresistant phenotype after treatment with B7-H1 siRNA. Conversely, breast and prostate carcinoma cells with minimal PI(3) kinase activation adopt an immunoresistant phenotype when engineered to overexpress B7-H1 protein. These observations describe a mechanism for immune escape from tumor dormancy in humans that relates to oncogenesis.

Organisms vary in the timing of energy acquisition and use for reproduction. Thus, breeding strategies exist on a continuum, from capital breeding to income breeding. Capital breeders acquire and store energy for breeding before the start of the reproductive season, while income breeders finance reproduction using energy acquired during the reproductive season. Latitude and its associated environmental drivers are expected to heavily influence breeding strategy, potentially leading to latitudinal variation in breeding strategies within a single species. We examined the breeding strategy of the Asian shore crab Hemigrapsus sanguineus at five sites spanning nearly 10° of latitude across its invaded United States range. We hypothesized that the primary breeding strategy of this species would shift from income breeding to capital breeding as latitude increases. We found that though this species’ breeding strategy is dominated by capital breeding throughout much of the range, income breeding increases in importance at lower latitudes. This latitudinal pattern is likely heavily influenced by the duration of the foraging and breeding seasons, which also vary with latitude. We also found that reproductive characteristics at the northern and southern edges of the invaded range were consistent with continued range expansion. We suggest that the reproductive flexibility of the Asian shore crab is a key facilitator of its continued invasion success. Our results highlight the influence of latitude on the breeding strategy of a species and emphasize the need for further research regarding the ecological importance and implications of flexibility in breeding strategies within species.

Infiltrating low grade gliomas (LGGs) are heterogeneous in their behavior and the strategies used for clinical management are highly variable. A key factor in clinical decision-making is that patients with mutations in the isocitrate dehydrogenase 1 and 2 (IDH1/2 ) oncogenes are more likely to have a favorable outcome and be sensitive to treatment. Because of their relatively long overall median survival, more aggressive treatments are typically reserved for patients that have undergone malignant progression (MP) to an anaplastic glioma or secondary glioblastoma (GBM). In the current study, ex vivo metabolic profiles of image-guided tissue samples obtained from patients with newly diagnosed and recurrent LGG were investigated using proton high-resolution magic angle spinning spectroscopy ( 1 H HR-MAS). Distinct spectral profiles were observed for lesions with IDH- mutated genotypes, between astrocytoma and oligodendroglioma histologies, as well as for tumors that had undergone MP. Levels of 2-hydroxyglutarate (2HG) were correlated with increased mitotic activity, axonal disruption, vascular neoplasia, and with several brain metabolites including the choline species, glutamate, glutathione, and GABA. The information obtained in this study may be used to develop strategies for in vivo characterization of infiltrative glioma, in order to improve disease stratification and to assist in monitoring response to therapy.

Aim Much research has quantified species responses to human‐modified ecosystems. However, there is limited work on how human‐modified ecosystems may reshape competitive interactions between species. Using a 19‐year study across 3 million ha, we aimed to answer the question: Are levels of interference competition between bird species context dependent and influenced by habitat structure and productivity? We focussed on the hyper‐aggressive behaviour of the Noisy Miner (Manorina melanocephala), which is recognized as a key threatening process for other woodland bird species in Australia. Whether environmental conditions such as amount of forest cover and net primary productivity (NPP) mediate the Noisy Miners' impact remains untested at large spatiotemporal scales. Location Temperate woodlands of south‐eastern Australia. Methods We gathered data on bird site occupancy from repeated surveys of field sites and assembled satellite data on tree cover and NPP. We constructed Bayesian multi‐species occupancy/detection models of bird species in woodland patches and tested the fixed and interactive effects of Noisy Miner presence, the amount of tree cover, NPP, and time. We quantified the responses of 31 species, many with known interactions with the Noisy Miner documented previously at fine spatial scales. Results We identified negative associations between the Noisy Miner and 18 bird species, including, unexpectedly, both small and large bodied taxa. Site occupancy in some species was influenced by interactions between Noisy Miner presence and increasing amounts of tree cover or productivity. For some species, interference competition by the Noisy Miner is context‐dependent and mitigated by increasing tree cover and/or increasing NPP. Main Conclusions Our analyses revealed that woodland bird conservation in our study region will be promoted by protecting refugia characterized by areas of high NPP and high tree cover. Preventing vegetation clearing that reduces tree cover could reduce interference competition by the Noisy Miner on parts of the remaining woodland bird community, including species of conservation concern.

Nonlethal injury is a pervasive stress on individual animals that can affect large portions of a population at any given time. Yet most studies examine snapshots of injury at a single place and time, making the implicit assumption that the impacts of nonlethal injury are constant. We sampled Asian shore crabs Hemigrapsus sanguineus throughout their invasive North American range and from the spring through fall of 2020. We then documented the prevalence of limb loss over this space and time. We further examined the impacts of limb loss and limb regeneration on food consumption, growth, reproduction, and energy storage. We show that injury differed substantially across sites and was most common towards the southern part of their invaded range on the East Coast of North America. Injury also varied idiosyncratically across sites and through time. It also had strong impacts on individuals via reduced growth and reproduction, despite increased food consumption in injured crabs. Given the high prevalence of nonlethal injury in this species, these negative impacts of injury on individual animals likely scale up to influence population level processes (e.g., population growth), and may be one factor acting against the widespread success of this invader.

PurposeTo evaluate safety and efficacy of radiation segmentectomy (RS) with 90Y glass microspheres in patients with limited metastatic liver disease not amenable to resection or percutaneous ablation.MethodsPatients with ≤ 3 tumors treated with RS from 6/2015 to 12/2017 were included. Target tumor radiation dose was > 190 Gy based on medical internal radiation dose (MIRD) dosimetry. Tumor response, local tumor progression (LTP), LTP-free survival (LTPFS) and disease progression rate in the treated segment were defined using Choi and RECIST 1.1 criteria. Toxicities were evaluated using modified SIR criteria.ResultsTen patients with 14 tumors underwent 12 RS. Median tumor size was 3 cm (range 1.4–5.6). Median follow-up was 17.8 months (range 1.6–37.3). Response rates per Choi and RECIST 1.1 criteria were 8/8 (100%) and 4/9 (44%), respectively. Overall LTP rate was 3/14 (21%) during the study period. One-, two- and three-year LTPFS was 83%, 83% and 69%, respectively. Median LTPFS was not reached. Disease progression rate in the treated segment was 6/18 (33%). Median overall survival was 41.5 months (IQR 16.7–41.5). Median delivered tumor radiation dose was 293 Gy (range 163–1303). One major complication was recorded in a patient post-Whipple procedure who suffered anaphylactic reaction to prophylactic cefotetan and liver abscess in RS region 6.5 months post-RS. All patients were alive on last follow-up.ConclusionRS of ≤ 3 hepatic segments can safely provide a 2-year local tumor control rate of 83% in selected patients with limited metastatic liver disease and limited treatment options. Optimal dosimetry methodology requires further investigation.

Regeneration of lost appendages is a gradual process in many species, spreading energetic costs of regeneration through time. Energy allocated to the regeneration of lost appendages cannot be used for other purposes and, therefore, commonly elicits energetic trade‐offs in biological processes. We used limb loss in the Asian shore crab Hemigrapsus sanguineus to compare the strength of energetic trade‐offs resulting from historic limb losses that have been partially regenerated versus current injuries that have not yet been repaired. Consistent with previous studies, we show that limb loss and regeneration results in trade‐offs that reduce reproduction, energy storage, and growth. As may be expected, we show that trade‐offs in these metrics from historic limb losses far outweigh trade‐offs from current limb losses, and correlate directly with the degree of historic limb loss that has been regenerated. As regenerating limbs get closer to their normal size, these historical injuries get harder to detect, despite the continued allocation of additional resources to limb development. Our results demonstrate the importance of and a method for identifying historic appendage losses and of quantifying the amount of regeneration that has already occurred, as opposed to assessing only current injury, to accurately assess the strength of energetic trade‐offs in animals recovering from nonlethal injury. We show that trade‐offs from previously lost limbs far outweigh trade‐offs from currently missing limbs or limbs that have begun to regenerate. Our results highlight the need to measure historical injury and recovery in order to fully understand energetic trade‐offs in biological systems where nonlethal injury is common.

This study reports on a preliminary evaluation of a cognitive behavioural intervention to improve social recovery among young people in the early stages of psychosis showing persistent signs of poor social functioning and unemployment. The study was a single-blind randomized controlled trial (RCT) with two arms, 35 participants receiving cognitive behaviour therapy (CBT) plus treatment as usual (TAU), and 42 participants receiving TAU alone. Participants were assessed at baseline and post-treatment. Seventy-seven participants were recruited from secondary mental health teams after presenting with a history of unemployment and poor social outcome. The cognitive behavioural intervention was delivered over a 9-month period with a mean of 12 sessions. The primary outcomes were weekly hours spent in constructive economic and structured activity. A range of secondary and tertiary outcomes were also assessed. Intention-to-treat analysis on the combined affective and non-affective psychosis sample showed no significant impact of treatment on primary or secondary outcomes. However, analysis of interactions by diagnostic subgroup was significant for secondary symptomatic outcomes on the Positive and Negative Syndrome Scale (PANSS) [F(1, 69)=3.99, p=0.05]. Subsequent exploratory analyses within diagnostic subgroups revealed clinically important and significant improvements in weekly hours in constructive and structured activity and PANSS scores among people with non-affective psychosis. The primary study comparison provided no clear evidence for the benefit of CBT in a combined sample of patients. However, planned analyses with diagnostic subgroups showed important benefits for CBT among people with non-affective psychosis who have social recovery problems. These promising results need to be independently replicated in a larger, multi-centre RCT.

Background: The Reducing Air Pollution in Detroit Intervention Study (RAPIDS) was designed to evaluate cardiovascular health benefits and personal fine particulate matter (particulate matter < 2.5 μm in diameter, PM2.5) exposure reductions via portable air filtration units (PAFs) among older adults in Detroit, Michigan. This double-blind randomized crossover intervention study has shown that, compared to sham, air filtration for 3 days decreased 3-day average brachial systolic blood pressure by 3.2 mmHg. The results also showed that commercially available HEPA-type and true HEPA PAFs mitigated median indoor PM2.5 concentrations by 58% and 65%, respectively. However, to our knowledge, no health intervention study in which a significant positive health effect was observed has also evaluated how outdoor and indoor PM2.5 sources impacted the subjects. With that in mind, detailed characterization of outdoor and indoor PM2.5 samples collected during this study and a source apportionment analysis of those samples using a positive matrix factorization model were completed. The aims of this most recent work were to characterize the indoor and outdoor sources of the PM2.5 this community was exposed to and to assess how effectively commercially available HEPA-type and true HEPA PAFs were able to reduce indoor and outdoor PM2.5 source contributions. Methods: Approximately 24 h daily indoor and outdoor PM2.5 samples were collected on Teflon and Quartz filters from the apartments of 40 study subjects during each 3-day intervention period. These filters were analyzed for mass, carbon, and trace elements. Environmental Protection Agency Positive Matrix Factorization (PMF) 5.0 was utilized to determine major emission sources that contributed to the outdoor and indoor PM2.5 levels during this study. Results: The major sources of outdoor PM2.5 were secondary aerosols (28%), traffic/urban dust (24%), iron/steel industries (15%), sewage/municipal incineration (10%), and oil combustion/refinery (6%). The major sources of indoor PM2.5 were organic compounds (45%), traffic + sewage/municipal incineration (14%), secondary aerosols (13%), smoking (7%), and urban dust (2%). Infiltration of outdoor PM2.5 for sham, HEPA-type, and true HEPA air filtration was 79 ± 24%, 61 ± 32%, and 51 ± 34%, respectively. Conclusions: The results from our study showed that intervention with PAFs was able to significantly decrease indoor PM2.5 derived from outdoor and indoor PM2.5 sources. The PAFs were also able to significantly reduce the infiltration of outdoor PM2.5. The results of this study provide insights into what types of major PM2.5 sources this community is exposed to and what degree of air quality and systolic blood pressure improvements are possible through the use of commercially available PAFs in a real-world setting.

The authors investigated whether the re-emergence of hopeless/suicidal cognitions over time can be explained within a differential activation framework. Studies 1 ( N  = 146) and 2 ( N  = 136) showed that individuals who reported suicidal ideation when depressed in the past had higher scores on the hopelessness/suicidality subscale of a measure assessing cognitive reactivity to low mood, the LEIDS. Study 3 ( N  = 32) demonstrated that self-reports on this subscale predicted changes in generativity for positive future events, an experimental measure of processes underlying hopelessness/suicidality, following sad mood induction. The results provide preliminary evidence that history of suicidal ideation is related to a specific cognitive response pattern, which may be reactivated by mild fluctuations in mood.