The male gamete membrane protein DMP9/DAU2 is required for double fertilization in flowering plants.

All flowering plants exhibit a unique type of sexual reproduction called 'double fertilization' in which each pollen tube-delivered sperm cell fuses with an egg and a central cell. Proteins that localize to the plasma membrane of gametes regulate one-to-one gamete pairing and fusion between male and female gametes for successful double fertilization. Here, we have identified a membrane protein from Lilium longiflorum generative cells using proteomic analysis and have found that the protein is an ortholog of Arabidopsis DUF679 DOMAIN MEMBRANE PROTEIN 9 (DMP9)/DUO1-ACTIVATED UNKNOWN 2 (DAU2). The flowering plant DMP9 proteins analyzed in this study were predicted to have four transmembrane domains and be specifically expressed in both generative and sperm cells. Knockdown of DMP9 resulted in aborted seeds due to single fertilization of the central cell. Detailed imaging of DMP9-knockdown sperm cells during in vivo and semi-in vitro double fertilization revealed that DMP9 is involved in gamete interaction that leads to correct double fertilization.

Multidisciplinary Approach to Prevent de novo Hepatitis B in Patients with Rheumatoid Arthritis.

The reactivation of hepatitis B virus (HBV) in patients with rheumatoid arthritis (RA) is currently a social problem. Our hospital has established a project team, which consisted of medical staff including doctors, nurses, pharmacists, and technicians, to prevent HBV reactivation and subsequent de novo hepatitis B in 2015. To verify the usefulness of the team, we aimed to examine the implementation rate of HBV screening tests in patients with RA in 2011, 2015, and 2018. We also examined the rate of HBV infection, as well as the rate of HBV reactivation during the course. In this study, medical records of patients who visited our hospital in 2011, 2015, and 2018 were retrospectively reviewed. HBV screening was completed when hepatitis B surface antigen (HBsAg), hepatitis B surface antibody (HBsAb), and hepatitis B core antibody (HBcAb) were all examined. The prevalence of patients who completed HBV screening dramatically increased from 2.4% in 2011 to 79.1% in 2015 and 86.9% in 2018. Patients who completed the screening had significantly higher rates of liver dysfunction, methotrexate use, and use of biological disease-modifying antirheumatic drugs than those who did not. Of the 767 patients who completed HBV screening in 2018, 157 patients (20.5%) had previously resolved HBV infection (HBsAg-negative but HBsAb- and/or HBcAb-positive). During a mean follow-up of 41.0 months, reactivation of HBV was observed in 10 out of the 157 patients (6.4%); however, none developed de novo hepatitis B. In conclusion, our multidisciplinary approach to prevent de novo hepatitis B is considered useful.

Applications of nutritional functional units in commodity-level life cycle assessment (LCA) of agri-food systems.

PURPOSE: The nutritional quality of final products is attracting an increased level of attention within life cycle assessment (LCA) literature of agri-food systems. The majority of these studies, however, are based on comparisons at the dietary level and, therefore, are unable to offer immediate implications for farmers as to how best to produce food. This article evaluates recent literature examining the nutrition-environment nexus at the commodity level, with the aim to identify potential pathways towards sustainability analysis that can inform both consumers and producers. METHODS: A systematic search of literature was carried out to produce a shortlist of studies, and strict exclusion criteria were applied to them afterwards to eliminate irrelevant material. The studies thus selected were classified into one of three tiers based on the level of complexity with regard to their functional units: (1) based on single nutrients, (2) based on composite indicators derived from multiple nutrients and (3) based on commodity-level analysis in a dietary context. RESULTS AND DISCUSSION: Sixteen papers were identified for inclusion in the review. All of them accounted for climate change either directly or indirectly, whilst only five addressed different impact categories at the same time. Nine studies estimated environmental impacts under functional units associated with nutrient density scores, and the others utilised alternative approaches to account for nutritional value such as linear programming and end-point modelling combined with epidemiological data. A recently developed method to calculate the marginal contribution of a commodity to the overall nutritional value of a specific diet was considered to be a successful first step in bridging the aforementioned knowledge gap. CONCLUSIONS: The LCA community should continue the ongoing effort to link farm management decisions to diet-level environmental impacts through an enhanced focus on human nutrition across the entire value chain. Future research comparing environmental performances of multiple food groups or multiple production systems should acknowledge differences in nutritional composition and bioavailability between the final products and, ideally, the effects of these nutrients on overall dietary quality.

Association between BACH2 expression and clinical prognosis in diffuse large B-cell lymphoma.

BACH2, a B cell-specific transcriptional repressor, plays a significant role in B cell maturation. Despite a number of previous studies, the clinicopathological significance of BACH2 expression in diffuse large B cell lymphoma (DLBCL) remains to be established. The present study was performed to validate the significance of BACH2 expression as a predictor of prognosis in DLBCL. A total of 94 DLBCL cases were included in the present study. All were diagnosed between 2008 and 2011, and thorough clinical and pathological investigations were possible, including immunohistochemical analysis of BACH2. Eighteen cases were selected by positive MYC gene alteration (MYC+ group) according to cytogenetic study. The remaining 76 cases were subclassified into germinal center B cell phenotype (GCB group, 38 cases) or non-GCB phenotype (non-GCB group, 38 cases). There were no significant differences between the two groups with regard to clinical characteristics and outcomes. In the GCB group, 21 cases were judged to have high BACH2 expression, with 19 cases in the non-GCB group. In cases with high BACH2 expression in GCB and non-GCB groups, the 3-year overall survival (OS) rate was significantly shorter than that with low expression (71.7% vs 91.3%, P = 0.0256). In the MYC+ group, 15 cases had high BACH2 expression levels. Although overall the MYC+ group showed short survival time (3-year OS 35.0%), 3 out of 4 cases with low BACH2 expression are alive without disease relapse at the time of publication of this paper. In conclusion, BACH2 expression level is a promising predictor of prognosis for DLBCL.

GATA2 regulates differentiation of bone marrow-derived mesenchymal stem cells.

The bone marrow microenvironment comprises multiple cell niches derived from bone marrow mesenchymal stem cells. However, the molecular mechanism of bone marrow mesenchymal stem cell differentiation is poorly understood. The transcription factor GATA2 is indispensable for hematopoietic stem cell function as well as other hematopoietic lineages, suggesting that it may maintain bone marrow mesenchymal stem cells in an immature state and also contribute to their differentiation. To explore this possibility, we established bone marrow mesenchymal stem cells from GATA2 conditional knockout mice. Differentiation of GATA2-deficient bone marrow mesenchymal stem cells into adipocytes induced accelerated oil-drop formation. Further, GATA2 loss- and gain-of-function analyses based on human bone marrow mesenchymal stem cells confirmed that decreased and increased GATA2 expression accelerated and suppressed bone marrow mesenchymal stem cell differentiation to adipocytes, respectively. Microarray analysis of GATA2 knockdowned human bone marrow mesenchymal stem cells revealed that 90 and 189 genes were upregulated or downregulated by a factor of 2, respectively. Moreover, gene ontology analysis revealed significant enrichment of genes involved in cell cycle regulation, and the number of G1/G0 cells increased after GATA2 knockdown. Concomitantly, cell proliferation was decreased by GATA2 knockdown. When GATA2 knockdowned bone marrow mesenchymal stem cells as well as adipocytes were cocultured with CD34-positive cells, hematopoietic stem cell frequency and colony formation decreased. We confirmed the existence of pathological signals that decrease and increase hematopoietic cell and adipocyte numbers, respectively, characteristic of aplastic anemia, and that suppress GATA2 expression in hematopoietic stem cells and bone marrow mesenchymal stem cells.

Interstitial Lung Disease With Respiratory Failure After COVID-19 mRNA Vaccination.

A septuagenarian woman developed dyspnea on the day following a fifth vaccination. Just before vaccination, a chest X-ray showed no abnormalities, but after the fifth vaccination, bilateral diffuse ground-glass opacities were detected. Bronchoalveolar lavage revealed a lymphocyte predominance and transbronchial lung biopsy revealed growth of the alveolar epithelium, along with organized polypoid granulation tissues in the alveolar ducts and bronchioles. Despite the administration of corticosteroids, imaging revealed persistent fibrosis, and she required long-term oxygen therapy. Although recent reports indicated that corticosteroids are effective for drug-induced interstitial lung disease related to COVID-19 mRNA vaccination, this case presented a somewhat different clinical manifestation.

Modeling of a tissue expander with a radiofrequency identification port in postmastectomy radiation therapy planning.

The purpose of this study was to evaluate the dose attenuation of Motiva Flora® (Flora, Establishment Labs, Alajuela, Costa Rica) tissue expander with a radiofrequency identification port locator and to develop a model for accurate postmastectomy radiation therapy planning. Dose attenuation was measured using an EBT3 film (Ashland, Bridgewater, NJ), and the optimal material and density assignment for the radiofrequency identification coil for dose calculation were investigated using the AcurosXB algorithm on the Eclipse (Varian Medical Systems, Palo Alto, CA) treatment planning system. Additionally, we performed in vivo dosimetry analysis using irradiation tangential to the Flora tissue expander to validate the modeling accuracy. Dose attenuations downstream of the Flora radiofrequency identification coil was 1.29% for a 6 MV X-ray and 0.99% for a 10 MV X-ray when the coil was placed perpendicular to the beam. The most suitable assignments for the material and density of the radiofrequency identification coil were aluminum and 2.27 g/cm3, respectively, even though the coil was actually made of copper. Gamma analysis of in vivo dosimetry with criteria of 3% and 2 mm did not fail in the coil region. Therefore, we conclude that the model is reasonable for clinical use.

Prevalence of Plastic and Hardware Foreign Bodies among Goats at Malawi Markets.

Smallholder goat production plays a major role in rural livelihoods and food security in Malawi, but suffers from drastic and unpredictable production losses. While goat production is closely linked to small-scale local markets for slaughter and butchering, the perspectives of butchers and their potential as a source of animal health information are largely untapped. Butchers can provide insights into goat health status at slaughter as well as issues that go unseen before slaughter, such as the presence of indigestible foreign bodies (IFBs). IFBs include solid materials such as plastics and hardware (metals, stones, and other hard objects) that cause foreign body syndrome and can lead to impaction, oedema, malnutrition, and death. To estimate the presence of IFBs, 150 market stand butchers were surveyed across five districts in Malawi, focusing on a distinction between hardware and single-use plastics, which are still widely present in Malawi despite bans on production. Most butchers found plastic IFBs (80.7%), with over half (56.7%) reporting plastic IFBs recently among the past five slaughters. Hardware IFBs were less common, reported by 45.3% of butchers. While some butchers commented on the impact of IFBs on meat quality metrics ex-post, the majority observed no differences. While butchers unanimously considered health to be an important characteristic when sourcing goats, 70.7% consider injury status to be less important or not important. Overall, this study highlights the issue of anthropogenic waste pollution on goat production in Malawi and demonstrates the potential for the surveillance of goat health at market.

Opportunities to improve goat production and food security in Botswana through forage nutrition and the use of supplemental feeds.

Goats fulfil a central role in food and nutritional security across Africa with over half of households owning or rearing goats in rural areas. However, goat performance is poor and mortality high. This study assessed the nutritional quality of commonly used feeds and proposes feed-baskets to enhance goat nutrition and health. Feeds were collected from 11 areas within the Central District of Botswana, and macronutrient analyses were conducted, including crude protein, fibre fractions, ash, and metabolizable energy (ME). Forage nutrition was compared across seasons and soil types. Additionally, seasonal supplementation trials were conducted to evaluate consumption rates of various supplements, including crop residues, pellets, Lablab purpureus, and Dichrostachys cinerea. Each supplement was provided ad libitum for a 24-h period, and consumption rates determined. Findings revealed significant differences in nutrition among various feed sources, across seasons, and in relation to soil types (p < 0.001). Consumption rates of supplements were higher during the dry season, possibly due to reduced forage availability. Supplement consumption rates varied across supplement type, with crop residues accounting for approximately 1% of dry matter intake, compared to up to 45% for pellets, 13% for L. purpureus, and 15% for D. cinerea. While wet season feed baskets exhibited higher ME values compared to dry-season feed-baskets, the relative impact of supplementation was more pronounced during the dry season. These results highlight the potential for optimizing goat diets through improved grazing and browsing management, especially during the reduced nutritional availability in the dry season in Botswana. Such diet optimisation may improve goat health and productivity, which may positively impact the food and financial security of smallholders by providing both increased yields and increased resilience. Importantly, rural communities can experience some of the lowest food security levels in the region. The interventions explored in this study utilise natural capital, often freely available, which can be deployed through existing husbandry systems, potentially making them accessible and practical to smallholders.

Stem water potential estimation from images using a field noise-robust deep regression-based approach in peach trees.

Field-grown peach trees are large and have a complex branch structure; therefore, detection of water deficit stress from images is challenging. We obtained large datasets of images of field-grown peach trees with continuous values of stem water potential (Ψstem) through partial secession treatment of the base of branches to change the water status of the branches. The total number of images as frames extracted from videos of branches was 23,181, 6743, and 10,752, in the training, validation, and test datasets, respectively. These datasets enabled us to precisely model water deficit stress using a deep-learning-regression model. The predicted Ψstem of frames belonging to a single branch showed a Gaussian distribution, and the coefficient of determination between the measured and predicted values of Ψstem increased to 0.927 by averaging the predicted values of the frames in each video. This method of averaging the predicted values of frames in each video can automatically eliminate noise and summarize data into the representative value of a tree and is considered to be robust for the diagnosis of water deficit stress in large field-grown peach trees with a complex branch structure.

Behavior of Male Gamete Fusogen GCS1/HAP2 and the Regulation in Arabidopsis Double Fertilization.

In the sexual reproduction of flowering plants, two independent fertilization events occur almost simultaneously: two identical sperm cells fuse with either the egg cell or the central cell, resulting in embryo and endosperm development to produce a seed. GCS1/HAP2 is a sperm cell membrane protein essential for plasma membrane fusion with both female gametes. Other sperm membrane proteins, DMP8 and DMP9, are more important for egg cell fertilization than that of the central cell, suggesting its regulatory mechanism in GCS1/HAP2-driving gamete membrane fusion. To assess the GCS1/HAP2 regulatory cascade in the double fertilization system of flowering plants, we produced Arabidopsis transgenic lines expressing different GCS1/HAP2 variants and evaluated the fertilization in vivo. The fertilization pattern observed in GCS1_RNAi transgenic plants implied that sperm cells over the amount of GCS1/HAP2 required for fusion on their surface could facilitate membrane fusion with both female gametes. The cytological analysis of the dmp8dmp9 sperm cell arrested alone in an embryo sac supported GCS1/HAP2 distribution on the sperm surface. Furthermore, the fertilization failures with both female gametes were caused by GCS1/HAP2 secretion from the egg cell. These results provided a possible scenario of GCS1/HAP2 regulation, showing a potential scheme for capturing additional GCS1/HAP2-interacting proteins.

Low-cost molecular methods to characterise gastrointestinal nematode co-infections of goats in Africa.

BACKGROUND: Veterinary diagnostics aid intervention strategies, track zoonoses, and direct selective breeding programs in livestock. In ruminants, gastrointestinal nematode (GIN) parasites are a major cause of production losses, but morphologically similar species limit our understanding of how specific GIN co-infections impact health in resource-limited settings. To estimate the presence and relative abundance of GINs and other helminths at the species level, we sought to develop a low-cost and low-resource molecular toolkit applied to goats from rural Malawi smallholdings. METHODS: Goats were subjected to health scoring and faecal sampling on smallholdings in Lilongwe district, Malawi. Infection intensities were estimated by faecal nematode egg counts with a faecal subsample desiccated for DNA analysis. Two DNA extraction methods were tested (low-resource magbead kit vs high-resource spin-column kit), with resulting DNA screened by endpoint polymerase chain reaction (PCR), semi-quantitative PCR, quantitative PCR (qPCR), high-resolution melt curve analysis (HRMC), and 'nemabiome' internal transcribed spacer 2 (ITS-2) amplicon sequencing. RESULTS: Both DNA isolation methods yielded comparable results despite poorer DNA purity and faecal contaminant carryover from the low-resource magbead method. GINs were detected in 100% of samples regardless of infection intensity. Co-infections with GINs and coccidia (Eimeria spp.) were present in most goats, with GIN populations dominated by Haemonchus contortus, Trichostrongylus colubriformis, Trichostrongylus axei, and Oesophagostomum columbianum. Both multiplex PCR and qPCR were highly predictive of GIN species proportions obtained using nemabiome amplicon sequencing; however, HRMC was less reliable than PCR in predicting the presence of particular species. CONCLUSIONS: These data represent the first 'nemabiome' sequencing of GINs from naturally infected smallholder goats in Africa and show the variable nature of GIN co-infections between individual animals. A similar level of granularity was detected by semi-quantitative PCR methods, which provided an accurate summary of species composition. Assessing GIN co-infections is therefore possible using cost-efficient low-resource DNA extraction and PCR approaches that can increase the capacity of molecular resources in areas where sequencing platforms are not available; and also open the door to affordable molecular GIN diagnostics. Given the diverse nature of infections in livestock and wildlife, these approaches have potential for disease surveillance in other areas.

Translating and applying a simulation model to enhance understanding of grassland management.

Each new generation of grassland managers could benefit from an improved understanding of how modification of nitrogen application and harvest dates in response to different weather and soil conditions will affect grass yields and quality. The purpose of this study was to develop a freely available grass yield simulation model, validated for England and Wales, and to examine its strengths and weaknesses as a teaching tool for improving grass management. The model, called LINGRA-N-Plus, was implemented in a Microsoft Excel spreadsheet and iteratively evaluated by students and practitioners (farmers, consultants, and researchers) in a series of workshops across the UK over 2 years. The iterative feedback led to the addition of new algorithms, an improved user interface, and the development of a teaching guide. The students and practitioners identified the ease of use and the capacity to understand, visualize and evaluate how decisions, such as variation of cutting intervals, affect grass yields as strengths of the model. We propose that an effective teaching tool must achieve an appropriate balance between being sufficiently detailed to demonstrate the major relationships (e.g., the effect of nitrogen on grass yields) whilst not becoming so complex that the relationships become incomprehensible. We observed that improving the user-interface allowed us to extend the scope of the model without reducing the level of comprehension. The students appeared to be interested in the explanatory nature of the model whilst the practitioners were more interested in the application of a validated model to enhance their decision making.

Are single global warming potential impact assessments adequate for carbon footprints of agri-food systems?

The vast majority of agri-food climate-based sustainability analyses use global warming potential (GWP100) as an impact assessment, usually in isolation; however, in recent years, discussions have criticised the 'across-the-board' application of GWP100 in Life Cycle Assessments (LCAs), particularly of food systems which generate large amounts of methane (CH4) and considered whether reporting additional and/or alternative metrics may be more applicable to certain circumstances or research questions (e.g. Global Temperature Change Potential (GTP)). This paper reports a largescale sensitivity analysis using a pasture-based beef production system (a high producer of CH4 emissions) as an exemplar to compare various climatatic impact assessments: CO2-equivalents using GWP100 and GTP100, and 'CO2-warming-equivalents' using 'GWP Star', or GWP*. The inventory for this system was compiled using data from the UK Research and Innovation National Capability, the North Wyke Farm Platform, in Devon, SW England. LCAs can have an important bearing on: (i) policymakers' decisions; (ii) farmer management decisions; (iii) consumers' purchasing habits; and (iv) wider perceptions of whether certain activities can be considered 'sustainable' or not; it is, therefore, the responsibility of LCA practitioners and scientists to ensure that subjective decisions are tested as robustly as possible through appropriate sensitivity and uncertainty analyses. We demonstrate herein that the choice of climate impact assessment has dramatic effects on interpretation, with GWP100 and GTP100 producing substantially different results due to their different treatments of CH4 in the context of carbon dioxide (CO2) equivalents. Given its dynamic nature and previously proven strong correspondence with climate models, out of the three assessments covered, GWP* provides the most complete coverage of the temporal evolution of temperature change for different greenhouse gas emissions. We extend previous discussions on the limitations of static emission metrics and encourage LCA practitioners to consider due care and attention where additional information or dynamic approaches may prove superior, scientifically speaking, particularly in cases of decision support.

Treatment planning comparison of high-dose-rate brachytherapy vs. robotic and conventional stereotactic body radiotherapy for ultrahypofractionated treatment of prostate cancer.

Background and purpose: Ultrahypofractionated radiation therapy is increasingly used in the treatment of prostate cancer. High-dose-rate brachytherapy (HDR-BT) and stereotactic body radiotherapy (SBRT) are representative methods of ultrahypofractionation. This study was performed to compare clinically applied treatment plans for patients who had been treated using HDR-BT vs. conventional or robotic SBRT. Materials and methods: Calculated dose-volume indices between HDR-BT without a perirectal spacer (n = 20), robotic SBRT without a spacer (n = 40), and conventional (non-robotic) SBRT with a spacer (n = 40) were compared. Percentages against the prescription dose regarding the planning target volume (PTV), bladder, rectum, and urethra were statistically compared. Results: The D50% of the PTV with HDR-BT (140.5% ± 4.9%) was significantly higher than that with robotic or conventional SBRT (116.2% ± 1.6%, 101.0% ± 0.4%, p < 0.01). The D2cm3 of the bladder with HDR-BT (65.6% ± 6.4%) was significantly lower than those with SBRT (105.3% ± 2.9%, 98.0% ± 1.3%, p < 0.01). The D2cm3 of the rectum with HDR-BT (60.6% ± 6.2%) was also significantly lower than those with SBRT (85.1% ± 8.8%, 70.4% ± 9.6%, p < 0.01). By contrast, the D0.1cm3 of the urethra with HDR-BT (117.1% ± 3.6%) was significantly higher than those with SBRT (100.2% ± 0.7%, 104.5% ± 0.6%, p < 0.01). Conclusions: HDR-BT could administer a higher dose to the PTV and a lower dose to the bladder and rectum, at the cost of a slightly higher dose to the urethra compared with SBRT.

Outcomes of adult patients with early T-cell precursor (ETP) acute lymphoblastic leukemia/lymphoma (ALL) and non-ETP T-ALL.

Early T-cell precursor (ETP) acute lymphoblastic leukemia/lymphoma (ALL) is generally considered to be a high-risk subtype. We retrospectively analyzed the clinical outcomes of adult patients diagnosed with ETP-ALL or other T-cell ALL (non-ETP T-ALL). The subjects were 82 patients (ETP-ALL: n = 18, non-ETP T-ALL: n = 64) for whom relevant immunophenotype data needed for classification were available. ETP-ALL patients were older (median age, 50.5 vs. 33.5 years, P = 0.042) and had less mediastinal involvement (27.8 vs. 73.4%, P < 0.001). The rate of complete remission (CR) with the first induction therapy was significantly lower in the ETP group (33.3 vs. 64.0%, P = 0.03), but the CR rate within 2 cycles of chemotherapy did not differ significantly (61.1 vs. 76.6%, P = 0.232). The 3-year overall survival (OS) rate was also similar in both groups (43.2 vs. 45.8%, P = 0.992). The ETP phenotype had no impact on survival in the transplant group or the non-transplant group. A multivariate analysis identified the male sex as a poor prognostic factor (HR: 4.43, P < 0.01), but not the immunophenotype of ETP. The prognosis for adult patients with ETP-ALL was comparable to that of non-ETP T-ALL patients. However, further studies aimed at improving the remission rate for ETP-ALL are needed.

Arable soil nitrogen dynamics reflect organic inputs via the extended composite phenotype.

Achieving food security requires resilient agricultural systems with improved nutrient-use efficiency, optimized water and nutrient storage in soils, and reduced gaseous emissions. Success relies on understanding coupled nitrogen and carbon metabolism in soils, their associated influences on soil structure and the processes controlling nitrogen transformations at scales relevant to microbial activity. Here we show that the influence of organic matter on arable soil nitrogen transformations can be decoded by integrating metagenomic data with soil structural parameters. Our approach provides a mechanistic explanation of why organic matter is effective in reducing nitrous oxide losses while supporting system resilience. The relationship between organic carbon, soil-connected porosity and flow rates at scales relevant to microbes suggests that important increases in nutrient-use efficiency could be achieved at lower organic carbon stocks than currently envisaged.

Dosimetric comparison between three-dimensional conformal radiotherapy followed by electron beam boost and volumetric modulated arc therapy using concomitant boost for the heart and cardiac segments in patients with left-sided breast cancer at risk for radiation-induced cardiac toxicity.

PURPOSE: We aimed to compare dosimetric parameters between three-dimensional conformal radiation therapy followed by electron beam boost (3D-CRT + EB) and volumetric modulated arc therapy using simultaneous integrated boost (SIB-VMAT) in left-sided breast cancer patients. METHODS: This study included 57 patients with left-sided breast cancer who underwent SIB-VMAT. All patients had a computed tomography-based maximum heart distance of ≥ 1 cm and were prescribed a dose of 42.56 Gy/16 fractions to the planning target volume and a concomitant-boosted target dose of 53.2 Gy or 51.2 Gy. The 3D-CRT + EB plan was retrospectively created for the purpose of comparison using tangential fields with field-in-field technique followed by electron beam irradiation. RESULTS: The doses to the clinical target volume significantly improved in the SIB-VMAT plans. All dosimetric parameters for the left anterior descending coronary artery (LAD) and LAD middle position (LAD mid) in the SIB-VMAT plans were significantly lower than those for 3D-CRT + EB plans (P < 0.01), while the doses to the heart, lung, contralateral breast and non-target tissue were decreased in the 3D-CRT + EB plans compared with those in the SIB-VMAT plans (e.g., 1.9 Gy vs. 2.9 Gy; P < 0.001 for the mean dose of heart). CONCLUSIONS: SIB-VMAT significantly improved the dose to the target while reducing the doses to the LAD and LAD mid, whereas 3D-CRT + EB significantly decreased the doses to the heart and other organs at risk in patients with left-sided breast cancer at risk for radiation-induced coronary artery disease.

HapMap scanning of novel human minor histocompatibility antigens.

Minor histocompatibility antigens (mHags) are molecular targets of allo-immunity associated with hematopoietic stem cell transplantation (HSCT) and involved in graft-versus-host disease, but they also have beneficial antitumor activity. mHags are typically defined by host SNPs that are not shared by the donor and are immunologically recognized by cytotoxic T cells isolated from post-HSCT patients. However, the number of molecularly identified mHags is still too small to allow prospective studies of their clinical importance in transplantation medicine, mostly due to the lack of an efficient method for isolation. Here we show that when combined with conventional immunologic assays, the large data set from the International HapMap Project can be directly used for genetic mapping of novel mHags. Based on the immunologically determined mHag status in HapMap panels, a target mHag locus can be uniquely mapped through whole genome association scanning taking advantage of the unprecedented resolution and power obtained with more than 3 000 000 markers. The feasibility of our approach could be supported by extensive simulations and further confirmed by actually isolating 2 novel mHags as well as 1 previously identified example. The HapMap data set represents an invaluable resource for investigating human variation, with obvious applications in genetic mapping of clinically relevant human traits.