Analyzing sustainability in bread production: a life cycle assessment approach to energy, exergy and environmental footprint.

Bread production is a pivotal component of global nutrition. However, its extensive production imposes significant strain on resources and energy, resulting in substantial environmental consequences. This study focuses on a multidimensional assessment of the environmental sustainability of the bread life cycle as a case study in Iran. By integrating four life cycle assessment (LCA) methods, this research demonstrates a comprehensive analysis of environmental effects, energy consumption, and exergy demand in bread production. It also identifies the hotspot stages and inputs within the bread production chain. Eventually, it proposes strategies for mitigating the environmental impacts in line with sustainable development goals. Data collection involved questionnaires by face-to-face interviews. The LCA evaluation was conducted using SimaPro software. Sustainability analysis was assessed using four different methods: CML, ReCiPe, cumulative energy demand (CED), and cumulative exergy demand (CExD) method, from cradle to bakery gate. The CML method results indicate that the highest environmental impacts are associated with marine aquatic ecotoxicity (157.04 to 193.36 kg 1,4-DB eq), fossil fuel depletion (11.05 to 12.73 MJ), eutrophication (4.20 × 10-3 to 4.70 × 10-3 kg PO4-3 eq), acidification (8.09 × 10-3 to 9.16 × 10-3 kg SO2 eq), and global warming (0.61 to 0.69 kg CO2 eq). The ReCiPe method highlights wheat production stages and gas consumption as the most significant contributors to damage in terms of human health, ecosystems, and resource consumption indicators. The CED method reveals that fossil energy accounts for over 97% of the energy consumed during the bread life cycle. Energy consumption per kilogram of bread ranges from 12.07 to 13.93 MJ. The CExD method for producing 1 kg of traditional bread falls between 32.25 and 35.88 MJ. More than 60% of this value is attributed to renewable resources of water used in irrigation during the wheat farming stage, while over 35% is linked to non-renewable fossil resources, primarily due to the consumption of natural gas in bakery operations. To assess the potential decrease in environmental emissions, a sensitivity analysis was performed, considering the effects of substituting natural gas with biogas and grid electricity with photovoltaic electricity in the bakery. Then, three improved scenarios were developed, each demonstrating effective reductions in environmental impacts, with the most remarkable decreases observed in marine aquatic ecotoxicity (55%) and fossil fuel depletion (44%). Overall, the findings demonstrate that Sangak bread production exhibits a more environmentally friendly profile than other types of bread. These results can guide decision-makers in the bread production industry towards implementing sustainable practices that prioritize resource efficiency and environmental conservation. Also, stakeholders can develop strategies to reduce the environmental impacts and work towards a more sustainable future.

Molecular dynamics (MD) study to predict performances of a novel hexanitrohexaazaisowurtzitane/1,4-dinitroimidazole (CL-20/1,4-DNI) energetic cocrystal under different temperatures.

CONTEXT: To estimate the influence of temperature on properties of 2,4,6,8,10,12-hexanitro- 2,4,6,8,10,12-hexaazaisowurtzitane/1,4-dinitroimidazole (CL-20/1,4-DNI) cocrystal explosive, the supercell crystal of CL-20/1,4-DNI cocrystal model was established. The mechanical properties, sensitivity, and stability of cocrystal model under different temperatures (T = 225 K, 250 K, 275 K, 300 K, 325 K, 350 K) were predicted. Results show that mechanical parameters, including bulk modulus, tensile modulus and shear modulus are the lowest when temperature is 300 K, while Cauchy pressure is the highest, indicating that CL-20/1,4-DNI cocrystal model has better mechanical properties at 300 K. Cohesive energy density (CED) and its components energies decrease monotonically with the increase of temperature, illustrating that the CL-20 and 1,4-DNI molecules are activated and the safety of cocrystal explosive is worsened with the increase of temperature. Cocrystal model has relatively higher binding energy when the temperature is 300 K, implying that the CL-20/1,4-DNI cocrystal explosive is more stable under this condition. METHODS: The CL-20/1,4-DNI cocrystal model was optimized and the properties were predicted through molecular dynamics (MD) method. The MD simulation was performed with COMPASS force field and the ensemble was set as NPT, external pressure was set as 0.0001 GPa.

Reflections of well-being: navigating body image, chronic energy deficiency, and nutritional intake among urban and rural adolescents.

Background: Adolescent growth and development is a period of very specific nutritional problems. As a result of poor growth and development, 36.3% of adolescents in Indonesia are at risk of developing CED. The purpose of this study was to determine the description of body image, the incidence of Chronic Energy Deficiency (CED), and nutritional intake in adolescents in urban and rural areas. Methods: This study used a descriptive quantitative design with a cross-sectional study conducted in Bandung and Sumedang on 387 adolescents aged 13-15 years. The instruments used in this study were body image questionnaire Figure Rating Scale (FRS) method, 2 × 24-h food recall, and anthropometry for Measuring mid upper arm circumference (MUAC). Results: Results of this study showed that more than half of adolescents in urban (54.0%) and rural areas (61.7%) were at risk of CED, had negative body image perceptions in urban (69.1%) and rural areas (62.3%), and underconsumption of macronutrients in both urban and rural adolescents. Conclusion: Most adolescents in urban and rural areas still consume less energy, carbohydrates, and protein. Perceived body image and nutrient intake contribute to the incidence of CED in adolescents.

CED-6/GULP and components of the clathrin-mediated endocytosis machinery act redundantly to correctly display CED-1 on the cell membrane in Caenorhabditis elegans.

CED-1 (cell death abnormal) is a transmembrane receptor involved in the recognition of "eat-me" signals displayed on the surface of apoptotic cells and thus central for the subsequent engulfment of the cell corpse in Caenorhabditis elegans. The roles of CED-1 in engulfment are well established, as are its downstream effectors. The latter include the adapter protein CED-6/GULP and the ATP-binding cassette family homolog CED-7. However, how CED-1 is maintained on the plasma membrane in the absence of engulfment is currently unknown. Here, we show that CED-6 and CED-7 have a novel role in maintaining CED-1 correctly on the plasma membrane. We propose that the underlying mechanism is via endocytosis as CED-6 and CED-7 act redundantly with clathrin and its adaptor, the Adaptor protein 2 complex, in ensuring correct CED-1 localization. In conclusion, CED-6 and CED-7 impact other cellular processes than engulfment of apoptotic cells.

Multiple Classification of Brain MRI Autism Spectrum Disorder by Age and Gender Using Deep Learning.

The fact that the rapid and definitive diagnosis of autism cannot be made today and that autism cannot be treated provides an impetus to look into novel technological solutions. To contribute to the resolution of this problem through multiple classifications by considering age and gender factors, in this study, two quadruple and one octal classifications were performed using a deep learning (DL) approach. Gender in one of the four classifications and age groups in the other were considered. In the octal classification, classes were created considering gender and age groups. In addition to the diagnosis of ASD (Autism Spectrum Disorders), another goal of this study is to find out the contribution of gender and age factors to the diagnosis of ASD by making multiple classifications based on age and gender for the first time. Brain structural MRI (sMRI) scans of participators with ASD and TD (Typical Development) were pre-processed in the system originally designed for this purpose. Using the Canny Edge Detection (CED) algorithm, the sMRI image data was cropped in the data pre-processing stage, and the data set was enlarged five times with the data augmentation (DA) techniques. The most optimal convolutional neural network (CNN) models were developed using the grid search optimization (GSO) algorism. The proposed DL prediction system was tested with the five-fold cross-validation technique. Three CNN models were designed to be used in the system. The first of these models is the quadruple classification model created by taking gender into account (model 1), the second is the quadruple classification model created by taking into account age (model 2), and the third is the eightfold classification model created by taking into account both gender and age (model 3). ). The accuracy rates obtained for all three designed models are 80.94, 85.42 and 67.94, respectively. These obtained accuracy rates were compared with pre-trained models by using the transfer learning approach. As a result, it was revealed that age and gender factors were effective in the diagnosis of ASD with the system developed for ASD multiple classifications, and higher accuracy rates were achieved compared to pre-trained models.

Investigating radiation profiles and conducting risk assessment for ecological and environmental components on Vaan and Koswari islands in the Tuticorin group of islands, India.

Natural radioactive concentration assessment was conducted on sediment, water, and biota obtained on Vaan and Koswari islands in the Tuticorin group of islands, Tamil Nadu, India. For biotic and abiotic components, radiation profiles such as gross alpha, beta, primordial radionuclide, polonium, and lead analyses were performed. The gross α and ß range from BDL to 15.18 ± 1.7 Bq/kg and 40.43 ± 4.9 Bq/kg to 105.12 ± 11.7 Bq/kg, respectively. Primordial radionuclides were analyzed using Nal(TI)-based scintillator with PC-MCA, and the concentrations ranged from 13.43 ± 3.3 Bq/kg to 30.97 ± 9.6 Bq/kg with a mean of 21.31 ± 2.7 Bq/kg for 238U; for 232Th, the values ranged from 11.09 ± 2.6 Bq/kg to 33.55 ± 9.5 Bq/kg with an average value of 23.89 ± 3.7 Bq/kg; and for 40 K, the values are 93.33 ± 27.3 Bq/kg to 219.91 ± 39.6 Bq/kg with an average value of 148.27 ± 21.7 Bq/kg. The present study values are lesser than the world average values. 210Po and 210Pb concentrations with an average value were determined to be 33.13 Bq/L and 16.56 Bq/L, 47.55 Bq/L and 22.37 Bq/L in the water sample, and 50.437 Bq kg1 and 62.012 Bq kg1, 46.99 Bq/kg and 58.625 Bq/kg in sediments of Vaan island and Koswari island. The concentrations of 210Po and 210Pb of Pogonias cromis were 19.27 ± 1.5 Bq/kg and 8.27 ± 1.01 Bq/kg, Belonidae 28.54 ± 2.4 Bq/kg and 18.32 ± 2.3 Bq/kg, Lepisosteidae 18.68 ± 1.4 Bq/kg and 11.17 ± 1.8 Bq/kg. The committed effective dosage was determined to be 35.74-54.61 µSv/y for 210Po and 25.39-56.25 µSv/y for 210Pb, in which the 210Pb value is lower; however, the 210Po value is higher than the global average value. The annual committed effective dosage as well as the radiological hazard indices were assessed and found to be much below the global average and the recommended limit, respectively. This research provides an extensive analysis of natural background radiation and establishes a baseline report on the radiological profile of biotic and abiotic factors in the Tuticorin group of islands, namely Vaan and Koswari, in Tamil Nadu, India.

Caenorhabditis elegans RAC1/ced-10 mutants as a new animal model to study very early stages of Parkinson's disease.

Patients with Parkinson's disease (PD) display non-motor symptoms arising prior to the appearance of motor signs and before a clear diagnosis. Motor and non-motor symptoms correlate with progressive deposition of the protein alpha-synuclein (Asyn) both within and outside of the central nervous system, and its accumulation parallels neurodegeneration. The genome of Caenorhabditis elegans does not encode a homolog of Asyn, thus rendering this nematode an invaluable system with which to investigate PD-related mechanisms in the absence of interference from endogenous Asyn aggregation. CED-10 is the nematode homolog of human RAC1, a small GTPase needed to maintain the function and survival of dopaminergic neurons against human Asyn-induced toxicity in C. elegans. Here, we introduce C. elegans RAC1/ced-10 mutants as a predictive tool to investigate early PD symptoms before neurodegeneration occurs. Deep phenotyping of these animals reveals that, early in development, they displayed altered defecation cycles, GABAergic abnormalities and an increased oxidation index. Moreover, they exhibited altered lipid metabolism evidenced by the accumulation of lipid droplets. Lipidomic fingerprinting indicates that phosphatidylcholine and sphingomyelin, but not phosphatidylethanolamine or phosphatidylserine, were elevated in RAC1/ced-10 mutant nematodes. These collective characteristics reflect the non-motor dysfunction, GABAergic neurotransmission defects, upregulation of stress response mechanisms, and metabolic changes associated with early-onset PD. Thus, we put forward an easy-to-manipulate preclinical animal model to deepen our understanding of early-stage PD and accelerate the translational path for therapeutic target discovery.

The Bicêtre occlusion scale is well suited to assess the efficacy of the Contour embolization device.

BACKGROUND: The Contour Embolization Device (CED) is typically assessed using coiling angiographic outcomes. However, these scales do not address device-specific problematics. We evaluated the usability of the Bicêtre occlusion scale (BOS) with the CED. RESULTS: BOS scores can be analyzed as BOSS 0 = no residual flow, BOSS 1 = residual flow inside the CED but with complete neck-sealing, BOSS 2 = neck-remnant, BOSS 3 = aneurysm-remnant, BOSS 1 + 3 = contrast filling inside the device and aneurysmal sac without complete neck-sealing. CONCLUSION: BOS usage should be encouraged as it provides a more comprehensive assessment of the mechanism of CED occlusion, especially considering the potential prognostic value of the neck sealing assessment.

Evaluation of patient radiation dose and risk of cancer from CT examinations.

Computed tomography (CT) examinations have been increasingly requested and become the major sources of patient exposure. The cancer risk from CT scans is contingent upon the amount of absorbed dose of organs. This study aims to determine the organ doses and risk of cancer incidence and mortality from CT examinations at high dose (cumulative effective dose, CED ≥ 100 mSv) in a single day to low dose (CED < 100 mSv) from common CT procedures. Data were gathered from two academic centers of patients aged 15 to 75 years old performed CT examinations during the period of 5 years. CED and organ dose were calculated using Monte Carlo simulation software. Lifetime attributable risk (LAR) was determined following Biological Effects of Ionizing Radiation (BEIR) VII report based on life table and baseline cancer rates of Thai population. At high dose, the highest LAR for breast cancer incidence in young female was 82 per 100,000 exposed patients with breast dose of 148 mGy (CT whole abdomen). The highest LAR for liver cancer incidence in male patient was 72 per 100,000 with liver dose of 133 mGy (multiple CT scans). At low dose, the highest average LAR for breast cancer incidence in young female was 23 per 100,000 while for liver cancer incidence in male patients was 22 per 100,000 (CTA whole aorta). Even though the LAR of cancer incidence and mortality was less than 100 per 100,000, they should not be neglected. The risk of cancer incidence may be increased in later life, particularly in young patients.

PUF-8, a C. elegans ortholog of the RNA-binding proteins PUM1 and PUM2, is required for robustness of the cell death fate.

During C. elegans development, 1090 somatic cells are generated, of which 959 survive and 131 die, many through apoptosis. We present evidence that PUF-8, a C. elegans ortholog of the mammalian RNA-binding proteins PUM1 and PUM2, is required for the robustness of this 'survival and death' pattern. We found that PUF-8 prevents the inappropriate death of cells that normally survive, and we present evidence that this anti-apoptotic activity of PUF-8 is dependent on the ability of PUF-8 to interact with ced-3 (a C. elegans ortholog of caspase) mRNA, thereby repressing the activity of the pro-apoptotic ced-3 gene. PUF-8 also promotes the death of cells that are programmed to die, and we propose that this pro-apoptotic activity of PUF-8 may depend on the ability of PUF-8 to repress the expression of the anti-apoptotic ced-9 gene (a C. elegans ortholog of Bcl2). Our results suggest that stochastic differences in the expression of genes within the apoptosis pathway can disrupt the highly reproducible and robust survival and death pattern during C. elegans development, and that PUF-8 acts at the post-transcriptional level to level out these differences, thereby ensuring proper cell number homeostasis.

Local delivery of hrBMP4 as an anticancer therapy in patients with recurrent glioblastoma: a first-in-human phase 1 dose escalation trial.

BACKGROUND: This Phase 1 study evaluates the intra- and peritumoral administration by convection enhanced delivery (CED) of human recombinant Bone Morphogenetic Protein 4 (hrBMP4) - an inhibitory regulator of cancer stem cells (CSCs) - in recurrent glioblastoma. METHODS: In a 3 + 3 dose escalation design, over four to six days, fifteen recurrent glioblastoma patients received, by CED, one of five doses of hrBMP4 ranging from 0·5 to 18 mg. Patients were followed by periodic physical, neurological, blood testing, magnetic resonance imaging (MRI) and quality of life evaluations. The primary objective of this first-in-human study was to determine the safety, dose-limiting toxicities (DLT) and maximum tolerated dose (MTD) of hrBMP4. Secondary objectives were to assess potential efficacy and systemic exposure to hrBMP4 upon intracerebral infusion. RESULTS: Intra- and peritumoral infusion of hrBMP4 was safe and well-tolerated. We observed no serious adverse events related to this drug. Neither MTD nor DLT were reached. Three patients had increased hrBMP4 serum levels at the end of infusion, which normalized within 4 weeks, without sign of toxicity. One patient showed partial response and two patients a complete (local) tumor response, which was maintained until the most recent follow-up, 57 and 30 months post-hrBMP4. Tumor growth was inhibited in areas permeated by hrBMP4. CONCLUSION: Local delivery of hrBMP4 in and around recurring glioblastoma is safe and well-tolerated. Three patients responded to the treatment. A complete response and long-term survival occurred in two of them. This warrants further clinical studies on this novel treatment targeting glioblastoma CSCs. TRIAL REGISTRATION: ClinicaTrials.gov identifier: NCT02869243.

A gluten degrading probiotic Bacillus subtilis LZU-GM relieve adverse effect of gluten additive food and balances gut microbiota in mice.

Gluten accumulation damages the proximal small intestine and causes celiac disease (CeD) which has not been effectively treated except by using a gluten-free diet. In this study, strain Bacillus subtilis LZU-GM was isolated from Pakistani traditional fermented sourdough and could degrade 73.7% of gluten in 24 h in vitro. Strain LZU-GM was employed for practical application to investigate gluten degradation in mice models. The results showed that strain LZU-GM was colonized in mice and the survival rate was around 0.95 % (P < 0.0001). The gluten degradation was 3-fold higher in the small intestine of the strain LZU-GM treated mice group remaining 1511.96 ng/mL of gluten peptides than the untreated mice group (6500.38 ng/mL). Immunochemical analysis showed that gluten-treated mice established positive antigliadin antibodies (AGA) in serum (IgA, IgG, and anti-TG2 antibodies) as compared to the strain LZU-GM treatment group. Furthermore, the number of IFN-γ, TNF-α, IL-10, and COX-2 cells decrease in the lamina propria of the strain LZU-GM treatment group (P < 0.0001). Microbial community bar plot analysis showed that Lactobacillus, Dubosiella, and Enterococcus genera were restored and stabilized in the LZU-GM treatment group while Blautia and Ruminococcus were found lower. The oral gavage of probiotic strain LZU-GM might be useful for gluten metabolism in the intestine during digestion and would be a long-term dietary treatment for CeD management.

A cascade electro-dehydration process for simultaneous extraction and enrichment of uranium from simulated seawater.

Uranium extraction from seawater has become a crucial issue that has raised tremendous attention. The transport of water molecules along with salt ions through an ion-exchange membrane is a common phenomenon for typical electro-membrane processes such as selective electrodialysis (SED). In this study, a cascade electro-dehydration process was proposed for the simultaneous extraction and enrichment of uranium from simulated seawater by taking advantage of water transport through ion-exchange membranes and the high permselectivity of membranes for monovalent ions against uranate ions. The results indicated that the electro-dehydration effect in SED allowed 1.8 times the concentration of uranium with a loose structure CJMC-5 cation-exchange membrane at a current density of 4 mA/cm2. Thereafter, a cascade electro-dehydration by a combination of SED with conventional electrodialysis (CED) enabled approximately 7.5 times uranium concentration with the extraction yield rate reaching over 80% and simultaneously desalting the majority of salts. Overall, a cascade electro-dehydration is a viable approach, creating a novel route for highly effective uranium extraction and enrichment from seawater.

Theoretical Prediction on Properties of 3,4-Bisnitrofurazanfuroxan (DNTF) Crystal and its Polymer Bonded Explosives (PBXs) Through Molecular Dynamics (MD) Simulation.

CONTEXT: 3,4-Bisnitrofurazanfuroxan (DNTF) is a typical high energy density compound (HEDC), it has high crystal density and detonation parameters, but also high mechanical sensitivity. To decrease its mechanical sensitivity, the DNTF based polymer bonded explosives (PBXs) was designed. The pure DNTF crystal and PBXs models were established. The stability, sensitivity, detonation performance and mechanical properties of DNTF crystal and PBXs models were predicted. Results show that PBXs models containing fluorine rubber (F2311) and fluorine resin (F2314) have higher binding energy, meaning that DNTF/F2311 and DNTF/F2314 is relatively more stable. PBXs models have higher value of cohesive energy density (CED) than pure DNTF crystal, DNTF/F2311 and DNTF/F2314 have the highest value of CED, implying that the sensitivity of PBXs is effectively decreased, DNTF/F2311 and DNTF/F2314 is more insensitive. PBXs have lower crystal density and detonation parameters than DNTF, the energy density is declined, DNTF/F2314 has higher energetic performance than other PBXs. Compared with pure DNTF crystal, engineering moduli (tensile modulus, shear modulus, bulk modulus) of PBXs models are obviously decreased, but Cauchy pressure is increased, implying that the mechanical properties of PBXs is superior to pure DNTF component, the PBXs containing F2311 or F2314 have more preferable mechanical properties. Consequently, DNTF/F2311 and DNTF/F2314 have the best comprehensive properties and is more attractive among the designed PBXs, indicating that F2311 and F2314 are more advantageous and promising in ameliorating properties of DNTF. METHODS: The properties of DNTF crystal and PBXs models were predicted through molecular dynamics (MD) method under Materials Studio 7.0 package. The MD simulation was performed with isothermal-constant volume (NVT) ensemble, and the force field was chosen as COMPASS force field. The temperature was set as 295 K, the time step was 1 fs and the total MD simulation time was 2 ns.

DOT-1.1 (DOT1L) deficiency in C. elegans leads to small RNA-dependent gene activation.

Methylation of histone H3 at lysine 79 (H3K79) is conserved from yeast to humans and is accomplished by Dot1 (disruptor of telomeric silencing-1) methyltransferases. The C. elegans enzyme DOT-1.1 and its interacting partners are similar to the mammalian DOT1L (Dot1-like) complex. The C. elegans DOT-1.1 complex has been functionally connected to RNA interference. Specifically, we have previously shown that embryonic and larval lethality of dot-1.1 mutant worms deficient in H3K79 methylation was suppressed by mutations in the RNAi pathway genes responsible for generation (rde-4) and function (rde-1) of primary small interfering RNAs (siRNAs). This suggests that dot-1.1 mutant lethality is dependent on the enhanced production of some siRNAs. We have also found that this lethality is suppressed by a loss-of-function of CED-3, a conserved apoptotic protease. Here, we describe a comparison of gene expression and primary siRNA production changes between control and dot-1.1 deletion mutant embryos. We found that elevated antisense siRNA production occurred more often at upregulated than downregulated genes. Importantly, gene expression changes were dependent on RDE-4 in both instances. Moreover, the upregulated group, which is potentially activated by ectopic siRNAs, was enriched in protease-coding genes. Our findings are consistent with a model where in the absence of H3K79 methylation there is a small RNA-dependent activation of protease genes, which leads to embryonic and larval lethality. DOT1 enzymes' conservation suggests that the interplay between H3K79 methylation and small RNA pathways may exist in higher organisms.

Impact of Season and Other Factors on Initiation, Discontinuation, and Switching of Systemic Drug Therapy in Patients with Psoriasis: A Retrospective Study.

This study investigated whether systemic drug prescribing for psoriasis varies by season and other exacerbating factors. Eligible patients with psoriasis were assessed for each season for initiation, discontinuation, and switching of systemic drugs. A total of 360,787 patients were at risk of initiating any systemic drugs in 2016‒2019; 39,572 patients and 35,388 patients were at risk of drug discontinuation or switching to a biologic and a nonbiologic systemic drug, respectively. The initiation of biologic therapy in 2016‒2019 peaked in spring (1.28%), followed by summer (1.11%), fall (1.08%), and winter (1.01%). Nonbiologic systemic drugs followed a similar pattern. Those aged 30‒39 years, male, those with psoriatic arthritis, those who live in the South region, those who live in areas with lower altitudes, and those who live in areas with lower humidity had higher initiation with the same seasonality pattern. Discontinuation of biologic drugs peaked in summer, and switching of biologics was highest in spring. Season is associated with initiation, discontinuation, and switching, although seasonality pattern is less clear for nonbiologic systemic drugs. Approximately 14,280 more patients with psoriasis in the United States are estimated to initiate a biologic in spring than in other seasons, and over 840 more biologic users switched in spring than in winter. The findings may provide evidence for healthcare resource planning in psoriasis management.

Radiation exposure in acute myeloid leukaemia, diffuse large B-cell lymphoma, and multiple myeloma patients in the first year following diagnosis.

Purpose: Radiological examinations are critical in the evaluation of patients with haematological malignancies for diagnosis and treatment. Any dose of radiation has been shown in studies to be harmful. In this regard, we assessed the radiation exposure of 3 types of haematological malignancies (diffuse large B-cell lymphoma [DLBCL], acute myeloid leukaemia [AML], and multiple myeloma [MM]) in our centre during the first year after diagnosis. Material and methods: In the first year after diagnosis we retrospectively reviewed the radiation exposure data of 3 types of haematological malignancies (DLBCL, AML, and MM). The total and median CED value (cumulative effective radiation dose in millisieverts [mSv]) of each patient was used. Each patient's total and median estimated CED value was calculated using a web-based calculator and recorded in millisieverts (mSv). Results: The total radiation doses in one year after diagnosis (CED value) were 46.54 ± 37.12 (median dose: 36.2) in the AML group; 63.00 ± 42.05 (median dose: 66.4) in the DLBCL group; and 28.04 ± 19.81 (median dose: 26.0) in the MM group (p = 0.0001). There was a significant difference between DLBCL and MM groups. Conclusions: In all 3 haematological malignancies, the radiation exposure was significant, especially in the DBLCL group, within the first year of diagnosis. It is critical to seek methods to reduce these dosage levels. In diagnostic radiology, reference values must be established to increase awareness and self-control and reduce patient radiation exposure. This paper is also the first to offer thorough details on the subject at hand, and we think it can serve as a guide for further investigation.

Hepatic vessels segmentation using deep learning and preprocessing enhancement.

PURPOSE: Liver hepatic vessels segmentation is a crucial step for the diagnosis process in patients with hepatic diseases. Segmentation of liver vessels helps to study the liver internal segmental anatomy that helps in the preoperative planning of surgical treatment. METHODS: Recently, the convolutional neural networks (CNN) have been proved to be efficient for the task of medical image segmentation. The paper proposes an automatic deep learning-based system for liver hepatic vessels segmentation of Computed Tomography (CT) datasets from different sources. The proposed work focuses on the combination of different steps; it starts by a preprocessing step to improve the vessels appearance within the liver region of interest in the CT scans. Coherence enhancing diffusion filtering (CED) and vesselness filtering methods are used to improve vessels contrast and intensity homogeneity. The proposed U-net based network architecture is implemented with modified residual block to include concatenation skip connection. The effect of enhancement using filtering step was studied. Also, the effect of data mismatch used in training and validation is studied. RESULTS: The proposed method is evaluated using many CT datasets. Dice similarity coefficient (DSC) is used to evaluate the method. The average DSC score achieved a score 79%. CONCLUSIONS: The proposed approach succeeded to segment liver vasculature from the liver envelope accurately, which makes it as potential tool for clinical preoperative planning.

Multi-Targeted Neutron Capture Therapy Combined with an 18 kDa Translocator Protein-Targeted Boron Compound Is an Effective Strategy in a Rat Brain Tumor Model.

BACKGROUND: Boron neutron capture therapy (BNCT) has been adapted to high-grade gliomas (HG); however, some gliomas are refractory to BNCT using boronophenylalanine (BPA). In this study, the feasibility of BNCT targeting the 18 kDa translocator protein (TSPO) expressed in glioblastoma and surrounding environmental cells was investigated. METHODS: Three rat glioma cell lines, an F98 rat glioma bearing brain tumor model, DPA-BSTPG which is a boron-10 compound targeting TSPO, BPA, and sodium borocaptate (BSH) were used. TSPO expression was evaluated in the F98 rat glioma model. Boron uptake was assessed in three rat glioma cell lines and in the F98 rat glioma model. In vitro and in vivo neutron irradiation experiments were performed. RESULTS: DPA-BSTPG was efficiently taken up in vitro. The brain tumor has 16-fold higher TSPO expressions than its brain tissue. The compound biological effectiveness value of DPA-BSTPG was 8.43 to F98 rat glioma cells. The boron concentration in the tumor using DPA-BSTPG convection-enhanced delivery (CED) administration was approximately twice as high as using BPA intravenous administration. BNCT using DPA-BSTPG has significant efficacy over the untreated group. BNCT using a combination of BPA and DPA-BSTPG gained significantly longer survival times than using BPA alone. CONCLUSION: DPA-BSTPG in combination with BPA may provide the multi-targeted neutron capture therapy against HG.

Targeting the IL4 receptor with MDNA55 in patients with recurrent glioblastoma: Results of a phase IIb trial.

BACKGROUND: MDNA55 is an interleukin 4 receptor (IL4R)-targeting toxin in development for recurrent GBM, a universally fatal disease. IL4R is overexpressed in GBM as well as cells of the tumor microenvironment. High expression of IL4R is associated with poor clinical outcomes. METHODS: MDNA55-05 is an open-label, single-arm phase IIb study of MDNA55 in recurrent GBM (rGBM) patients with an aggressive form of GBM (de novo GBM, IDH wild-type, and nonresectable at recurrence) on their 1st or 2nd recurrence. MDNA55 was administered intratumorally as a single dose treatment (dose range of 18 to 240 ug) using convection-enhanced delivery (CED) with up to 4 stereo-tactically placed catheters. It was co-infused with a contrast agent (Gd-DTPA, Magnevist®) to assess distribution in and around the tumor margins. The flow rate of each catheter did not exceed 10µL/min to ensure that the infusion duration did not exceed 48 h. The primary endpoint was mOS, with secondary endpoints determining the effects of IL4R status on mOS and PFS. RESULTS: MDNA55 showed an acceptable safety profile at doses up to 240 µg. In all evaluable patients (n = 44) mOS was 11.64 months (80% one-sided CI 8.62, 15.02) and OS-12 was 46%. A subgroup (n = 32) consisting of IL4R High and IL4R Low patients treated with high-dose MDNA55 (>180 ug) showed the best benefit with mOS of 15 months, OS-12 of 55%. Based on mRANO criteria, tumor control was observed in 81% (26/32), including those patients who exhibited pseudo-progression (15/26). CONCLUSIONS: MDNA55 demonstrated tumor control and promising survival and may benefit rGBM patients when treated at high-dose irrespective of IL4R expression level.Trial Registration: Clinicaltrials.gov NCT02858895.