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T cells represent a crucial component of the adaptive immune system and mediate anti-tumoral immunity as well as protection against infections, including respiratory viruses such as SARS-CoV-2. Next-generation sequencing of the T-cell receptors (TCRs) can be used to profile the T-cell repertoire. We developed a customized pipeline for Network Analysis of Immune Repertoire (NAIR) with advanced statistical methods to characterize and investigate changes in the landscape of TCR sequences. We first performed network analysis on the TCR sequence data based on sequence similarity. We then quantified the repertoire network by network properties and correlated it with clinical outcomes of interest. In addition, we identified (1) disease-specific/associated clusters and (2) shared clusters across samples based on our customized search algorithms and assessed their relationship with clinical outcomes such as recovery from COVID-19 infection. Furthermore, to identify disease-specific TCRs, we introduced a new metric that incorporates the clonal generation probability and the clonal abundance by using the Bayes factor to filter out the false positives. TCR-seq data from COVID-19 subjects and healthy donors were used to illustrate that the proposed approach to analyzing the network architecture of the immune repertoire can reveal potential disease-specific TCRs responsible for the immune response to infection., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Yang, Cham, Neal, Fan, He and Zhang.)

Stereotactic ablative radiotherapy (SABR) commonly is used for small liver metastases. Modern conformal radiotherapy techniques, including 3-dimensional conformal radiotherapy and intensity-modulated radiation therapy, enable the safe delivery of SABR to small liver volumes. For larger tumors, the safe delivery of SABR can be challenging due to a more limited volume of healthy normal liver parenchyma and the proximity of the tumor to radiosensitive organs, such as the stomach, duodenum, and large intestine. Controlling respiratory motion, the use of image guidance, and increasing the number of radiation fractions sometimes are necessary for the safe delivery of SABR in these situations., Competing Interests: Disclosure P.B. Romesser reports research funding from and is a consultant for EMD Serono and has received travel support from Elekta., (Copyright © 2020 Elsevier Inc. All rights reserved.)

Addressing the global decline of coral reefs requires effective actions from managers, policymakers and society as a whole. Coral reef scientists are therefore challenged with the task of providing prompt and relevant inputs for science-based decision-making. Here, we provide a baseline dataset, covering 1300 km of tropical coral reef habitats globally, and comprised of over one million geo-referenced, high-resolution photo-quadrats analysed using artificial intelligence to automatically estimate the proportional cover of benthic components. The dataset contains information on five major reef regions, and spans 2012-2018, including surveys before and after the 2016 global bleaching event. The taxonomic resolution attained by image analysis, as well as the spatially explicit nature of the images, allow for multi-scale spatial analyses, temporal assessments (decline and recovery), and serve for supporting image recognition developments. This standardised dataset across broad geographies offers a significant contribution towards a sound baseline for advancing our understanding of coral reef ecology and thereby taking collective and informed actions to mitigate catastrophic losses in coral reefs worldwide.

Primary producers in terrestrial and marine systems can be affected by fungal pathogens threatening the provision of critical ecosystem services. Crustose coralline algae (CCA) are ecologically important members of tropical reef systems and are impacted by coralline fungal disease (CFD) which manifests as overgrowth of the CCA crust by fungal lesions causing partial to complete mortality of the CCA host. No natural controls for CFD have been identified, but nominally herbivorous fish could play a role by consuming pathogenic fungi. We documented preferential grazing on fungal lesions by adults of six common reef-dwelling species of herbivorous Acanthuridae and Labridae, (surgeonfish and parrotfish) which collectively demonstrated an ~ 80-fold higher grazing rate on fungal lesions relative to their proportionate benthic coverage, and a preference for lesions over other palatable substrata (e.g. live scleractinian coral, CCA, or algae). Furthermore, we recorded a ~ 600% increase in live CFD lesion size over an approximately 2-week period when grazing by herbivorous fish was experimentally excluded suggesting that herbivorous reef fish could control CFD progression by directly reducing biomass of the fungal pathogen. Removal rates may be sufficient to allow CCA to recover from infection and explain historically observed natural waning behaviour after an outbreak. Thus, in addition to their well-known role as determinants of macroalgal overgrowth of reefs, herbivorous fish could thus also be important in control of diseases affecting crustose coralline algae that stabilize the foundation of coral reef substrata.

Objectives: Patients with prior irradiated head and neck cancer (HNC) who are ineligible for definitive retreatment have limited local palliative options. We report the largest series of the use of the Quad Shot (QS) regimen as a last-line local palliative therapy., Materials and Methods: We identified 166 patients with prior HN radiation therapy (RT) treated with QS regimen (3.7 Gy twice daily over 2 consecutive days at 4 weeks intervals per cycle, up to 4 cycles). Palliative response defined by symptom(s) relief or radiographic tumor reduction, locoregional progression free survival (LPFS), overall survival (OS) and radiation-related toxicity were assessed., Results: Median age was 66 years. Median follow-up for all patients was 6.0 months and 9.7 months for living patients. Overall palliative response rate was 66% and symptoms improved in 60% of all patients. Predictors of palliative response were > 2 year interval from prior RT and 3-4 QS cycles. Median LPFS was 5.1 months with 1-year LPFS 17.7%, and median OS was 6.4 months with 1-year OS 25.3%. On multivariate analysis, proton RT, KPS > 70, presence of palliative response and 3-4 QS cycles were associated with improved LPFS and improved OS. The overall Grade 3 toxicity rate was 10.8% (n = 18). No Grade 4-5 toxicities were observed., Conclusion: Palliative QS is an effective last-line local therapy with minimal toxicity in patients with previously irradiated HNC. The administration of 3-4 QS cycles predicts palliative response, improved PFS, and improved OS. KPS > 70 and proton therapy are associated with survival improvements., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2020 Elsevier Ltd. All rights reserved.)

Background: The mesenchymal phenotype in glioblastoma (GBM) and other cancers drives aggressiveness and treatment resistance, leading to therapeutic failure and recurrence of disease. Currently, there is no successful treatment option available against the mesenchymal phenotype., Methods: We classified patient-derived GBM stem cell lines into 3 subtypes: proneural, mesenchymal, and other/classical. Each subtype's response to the inhibition of diacylglycerol kinase alpha (DGKα) was compared both in vitro and in vivo. RhoA activation, liposome binding, immunoblot, and kinase assays were utilized to elucidate the novel link between DGKα and geranylgeranyltransferase I (GGTase I)., Results: Here we show that inhibition of DGKα with a small-molecule inhibitor, ritanserin, or RNA interference preferentially targets the mesenchymal subtype of GBM. We show that the mesenchymal phenotype creates the sensitivity to DGKα inhibition; shifting GBM cells from the proneural to the mesenchymal subtype increases ritanserin activity, with similar effects in epithelial-mesenchymal transition models of lung and pancreatic carcinoma. This enhanced sensitivity of mesenchymal cancer cells to ritanserin is through inhibition of GGTase I and downstream mediators previously associated with the mesenchymal cancer phenotype, including RhoA and nuclear factor-kappaB. DGKα inhibition is synergistic with both radiation and imatinib, a drug preferentially affecting proneural GBM., Conclusions: Our findings demonstrate that a DGKα-GGTase I pathway can be targeted to combat the treatment-resistant mesenchymal cancer phenotype. Combining therapies with greater activity against each GBM subtype may represent a viable therapeutic option against GBM., (© The Author(s) 2017. Published by Oxford University Press on behalf of the Society for Neuro-Oncology. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com)

Massive declines in population abundances of marine animals have been documented over century-long time scales. However, analogous loss of spatial extent of habitat-forming organisms is less well known because georeferenced data are rare over long time scales, particularly in subtidal, tropical marine regions. We use high-resolution historical nautical charts to quantify changes to benthic structure over 240 years in the Florida Keys, finding an overall loss of 52% (SE, 6.4%) of the area of the seafloor occupied by corals. We find a strong spatial dimension to this decline; the spatial extent of coral in Florida Bay and nearshore declined by 87.5% (SE, 7.2%) and 68.8% (SE, 7.5%), respectively, whereas that of offshore areas of coral remained largely intact. These estimates add to finer-scale loss in live coral cover exceeding 90% in some locations in recent decades. The near-complete elimination of the spatial coverage of nearshore coral represents an underappreciated spatial component of the shifting baseline syndrome, with important lessons for other species and ecosystems. That is, modern surveys are typically designed to assess change only within the species' known, extant range. For species ranging from corals to sea turtles, this approach may overlook spatial loss over longer time frames, resulting in both overly optimistic views of their current conservation status and underestimates of their restoration potential.

Massive coral bleaching events associated with high sea surface temperatures are forecast to become more frequent and severe in the future due to climate change. Monitoring colony recovery from bleaching disturbances over multiyear time frames is important for improving predictions of future coral community changes. However, there are currently few multiyear studies describing long-term outcomes for coral colonies following acute bleaching events. We recorded colony pigmentation and size for bleached and unbleached groups of co-located conspecifics of three major reef-building scleractinian corals ( Orbicella franksi , Siderastrea siderea, and Stephanocoenia michelini ; n  = 198 total) in Bocas del Toro, Panama, during the major 2005 bleaching event and then monitored pigmentation status and changes live tissue colony size for 8 years (2005-2013). Corals that were bleached in 2005 demonstrated markedly different response trajectories compared to unbleached colony groups, with extensive live tissue loss for bleached corals of all species following bleaching, with mean live tissue losses per colony 9 months postbleaching of 26.2% (±5.4 SE ) for O. franksi, 35.7% (±4.7 SE ) for S. michelini , and 11.2% (±3.9 SE ) for S. siderea . Two species, O. franksi and S. michelini , later recovered to net positive growth, which continued until a second thermal stress event in 2010. Following this event, all species again lost tissue, with previously unbleached colony species groups experiencing greater declines than conspecific sample groups, which were previously bleached, indicating a possible positive acclimative response. However, despite this beneficial effect for previously bleached corals, all groups experienced substantial net tissue loss between 2005 and 2013, indicating that many important Caribbean reef-building corals will likely suffer continued tissue loss and may be unable to maintain current benthic coverage when faced with future thermal stress forecast for the region, even with potential benefits from bleaching-related acclimation.

Size and growth rates for individual colonies are some of the most essential descriptive parameters for understanding coral communities, which are currently experiencing worldwide declines in health and extent. Accurately measuring coral colony size and changes over multiple years can reveal demographic, growth, or mortality patterns often not apparent from short-term observations and can expose environmental stress responses that may take years to manifest. Describing community size structure can reveal population dynamics patterns, such as periods of failed recruitment or patterns of colony fission, which have implications for the future sustainability of these ecosystems. However, rapidly and non-invasively measuring coral colony sizes in situ remains a difficult task, as three-dimensional underwater digital reconstruction methods are currently not practical for large numbers of colonies. Two-dimensional (2D) planar area measurements from projection of underwater photographs are a practical size proxy, although this method presents operational difficulties in obtaining well-controlled photographs in the highly rugose environment of the coral reef, and requires extensive time for image processing. Here, we present and test the measurement variance for a method of making rapid planar area estimates of small to medium-sized coral colonies using a lightweight monopod image-framing system and a custom semi-automated image segmentation analysis program. This method demonstrated a coefficient of variation of 2.26% for repeated measurements in realistic ocean conditions, a level of error appropriate for rapid, inexpensive field studies of coral size structure, inferring change in colony size over time, or measuring bleaching or disease extent of large numbers of individual colonies.

Global climate change and other anthropogenic stressors have heightened the need to rapidly characterize ecological changes in marine benthic communities across large scales. Digital photography enables rapid collection of survey images to meet this need, but the subsequent image annotation is typically a time consuming, manual task. We investigated the feasibility of using automated point-annotation to expedite cover estimation of the 17 dominant benthic categories from survey-images captured at four Pacific coral reefs. Inter- and intra- annotator variability among six human experts was quantified and compared to semi- and fully- automated annotation methods, which are made available at coralnet.ucsd.edu. Our results indicate high expert agreement for identification of coral genera, but lower agreement for algal functional groups, in particular between turf algae and crustose coralline algae. This indicates the need for unequivocal definitions of algal groups, careful training of multiple annotators, and enhanced imaging technology. Semi-automated annotation, where 50% of the annotation decisions were performed automatically, yielded cover estimate errors comparable to those of the human experts. Furthermore, fully-automated annotation yielded rapid, unbiased cover estimates but with increased variance. These results show that automated annotation can increase spatial coverage and decrease time and financial outlay for image-based reef surveys.

Coral reefs globally are declining rapidly because of both local and global stressors. Improved monitoring tools are urgently needed to understand the changes that are occurring at appropriate temporal and spatial scales. Coral fluorescence imaging tools have the potential to improve both ecological and physiological assessments. Although fluorescence imaging is regularly used for laboratory studies of corals, it has not yet been used for large-scale in situ assessments. Current obstacles to effective underwater fluorescence surveying include limited field-of-view due to low camera sensitivity, the need for nighttime deployment because of ambient light contamination, and the need for custom multispectral narrow band imaging systems to separate the signal into meaningful fluorescence bands. Here we describe the Fluorescence Imaging System (FluorIS), based on a consumer camera modified for greatly increased sensitivity to chlorophyll-a fluorescence, and we show high spectral correlation between acquired images and in situ spectrometer measurements. This system greatly facilitates underwater wide field-of-view fluorophore surveying during both night and day, and potentially enables improvements in semi-automated segmentation of live corals in coral reef photographs and juvenile coral surveys.

When either electron or hole doped at concentrations x approximately 0.1, the LaFeAsO family displays remarkably high temperature superconductivity with Tc up to 55 K. In the most energetically stable Q-->M=(pi,pi,0) antiferromagnetic (AFM) phase comprised of tetragonal-symmetry breaking alternating chains of aligned spins, there is a deep pseudogap in the Fe 3d states centered at the Fermi energy arising from light carriers (m* approximately 0.25-0.33), and very strong magnetophonon coupling is uncovered. Doping (of either sign) beyond x approximately 0.08 results in heavy carriers per Fe (by roughly an order of magnitude) with a large Fermi surface. Calculated Fe-Fe transverse exchange couplings Jij(R) reveal that exchange coupling is strongly dependent on both the AFM symmetry and on the Fe-As distance.