Shigella flexneri causes bacillary dysentery by invading the colon epithe-lium, leading to inflammation and tissue damage. The emergence of multidrug-resistant (MDR) Shi-gella strains and the lack of effective vaccines have highlighted the need for alternative treatments. Natural plant compounds have been explored as potential antimicrobial agents. This study evaluates the antibacterial activity of ethanolic (70%-96%) and methanolic (70%-99.9%) extracts of Termi-nalia chebula Retz. against MDR S. flexneri and their effect on bacterial invasion of HeLa cells in vitro. We assessed the anti-MDR S. flexneri activity of these extracts by measuring minimum inhib-itory concentration (MIC) and minimum bactericidal concentration (MBC). Four Shigella strains belonging to various serotypes and resistant to multiple drugs were used in this study. The invasiveness of S. flexneri was assayed by plaque formation in HeLa cell culture under in vitro conditions. Ethanolic and methanolic extracts of Terminalia chebula Retz. were made in varying concentrations. The antibacterial effects of these extracts against MDR S. flexneri strains were evaluated by determining minimum inhibitory concentration (MIC) and min-imum bactericidal concentration (MBC). Plaque-forming assay confirmed that all four S. flexneri serotypes were highly invasive in HeLa cells. All the compounds screened herein were found to be antibacterial (MIC = 0.39-12.5 mg/mL) and (MBC = 0.78-25 mg/mL) against the multidrug-resistant invasive S. flexneri strain, while the MBC/MIC ratio showed both bactericidal and bacteriostatic activity. Shigella species are highly infectious and increasingly multidrug-resistant pathogens with significant invasive potential in intestinal cells, as confirmed by our HeLa cell plaque assay results, consistent with prior studies. Our investigation indicates that Terminalia chebula Retz. ex-tracts may exhibit antibacterial activity against multidrug-resistant invasive Shigella isolates. Com-parable research has reported similar antimicrobial effects of T. chebula against various resistant bac-teria, including Shigella sonnei, MRSA, and MDR Escherichia coli. While some studies found other plant extracts, such as Rhus javanica, more potent, bioactive compounds of T. chebula, such as gallic acid derivatives, support its promising role in combating antibiotic-resistant infections. These findings suggest that ethanolic and methanolic extracts of Terminalia chebula may have antimicrobial activity against multidrug-resistant and invasive Shigella flexneri. These pre-liminary results indicate that T. chebula extracts warrant further exploration as potential antimicrobial agents against MDR Shigella infections. However, given the limited sample size in this study, further research with larger and more diverse strains is necessary to confirm the therapeutic potential of these plant extracts.

Background. To reduce overweight and obesity rates, various Dutch municipalities applied healthy weight approaches (HWAs) that connect the medical and social domain. To strengthen HWAs and thus healthcare, learning communities (LCs) were implemented in 2021 that included multidisciplinary members like policy makers, care professionals, practice professionals and patients/citizens. LCs aim to stimulate learning, cross-sectoral collaboration, and actions on multiple levels and themes to leverage change. However, it is unclear whether LC actions contribute to applying actions to leverage change, and what the perceived LC impact is according LC members, while this determines adequate action implementation, and the continuation of LCs. Therefore, this study aims to gain insights into the perceived impact of these LCs on HWAs. Approach. This two-step study was performed among two LCs that had eight meetings each, and one steering committee that had two meetings. These meetings ended with creating action lists. First, we analyzed the action lists by identifying the corresponding themes and levels, running frequencies and ordinal regression analyses. Second, we thematically analyzed qualitative LC meeting evaluation questionnaires, and semi-structured interviews among LC members. Results. We present our pre-liminary results. In summary, actions targeted most themes and levels to leverage HWA change. Still, the themes ""knowledge exchange"" and ""combined forces"" were targeted the most. Some type of actions seemed more likely to be executed successfully; and some type of actions were more likely to be formulated throughout later LC meetings, which will be elaborated during the presentation. Members perceived LC impacts on the HWA regarding three main themes: “Ideas about the next steps toward solutions”, “More collaboration” and “Working more effectively”. Implications. Conducting action lists analyses and interviews gained insights into short term outcomes, which may be used during LC meetings to continuously adjust LCs, HWAs, and healthcare actions were necessary. Future research is recommended.

Circular saw inserts are fundamental and high-value-added cutting tool inserts used for sawing, slot milling, and other related machining processes. In their mass production, sintered blanks are first made by powder metallurgy and then precisely form-ground to generate the geometric shapes and dimensions required for cutting action. In order to ensure quality in the production of circular saw inserts, the defects of sintered blanks and geometric accuracy of semi-products must be inspected before and after the form-grinding process, respectively. To this end, this paper presents the preliminary development of an automated optical inspection (AOI) system for quality control of circular saw inserts. A prototype system was designed and constructed in this study. Image processing procedures were then developed to perform the calibration process of the prototype system, defect detection of the sintered blanks, and geometric measurement of the form-ground semi-products. Experiments were conducted to inspect insert samples and test the feasibility of the developed prototype system. Preliminary experimental results verified the presented prototype system and image processing procedures as being able to inspect certain circular saw inserts for ensuring quality control.

Abstract (analytical)Given the lack of evidence in this area, the general objective of this study was to describe and apply an instrument designed to measure children's rights in Chile based on the day to day practices of social operators who work with children and adolescents, in educational, health, justice and psychosocial development centers. The sample consisted of 407 participants (including teachers and psychologists). The instrument takes into account the four fundamental principles of the Convention onthe Rights of the Child: non-discrimination; the best interest of the child; the right to life, development and survival; and the right to be heard. The preliminary results suggest that there are statisticallysignificant differences in the degree of fulfillment of rights in relation to each fundamental principle. The internal consistency of the instrument, its adaptation to measure the fulfillment of each principleand the population that receive assistance are discussed, as well as application of the instrument with general and specific child populations. Keywords: State responsibility, children's rights, evaluation instruments, social workers.

A status report with preliminary results for the IndoBioSys project is presented and the impact of the project results for our knowledge of the Indonesian fauna is discussed. Using the REST API available on the Barcode of Life Data System we recover 21,153 public records (3,390 BINs) from Indonesia and compare against the 21,813 records (3,580 BINs) generated by the IndoBioSys project. From all IndoBioSys BINs, 3,366 (94%) are new to Indonesia. IndoBioSys is responsible for a BIN increase of 36.5% in Lepidoptera, 62.6% in Trichoptera, 986% in Coleoptera, and 1,086% in Hymenoptera. After two years of the IndoBioSys project, the Museum Zoologicum Bogoriense became the depository institution of 51.9% of Lepidoptera records, 95.8% of Coleoptera records, 97.6% of Hymenoptera records and 59.4% of Trichoptera records for Indonesia available on Barcode of Life Data System (BOLD). Now, with 55% of all Indonesian records available on BOLD, it is the most important depository for records of Indonesian genetic biodiversity, housing more than 23,000 new voucher specimens in their collections. Before IndoBioSys, the Museum Zoologicum Bogoriense was responsible for only 9% of all records available in the Barcode of Life Data System for Indonesia, showing the importance of those pipelines in empowering the local institutions in becoming the reference depository of the local fauna.

Age-related changes in organ function, immune dysregulation, and the effects of senescence explain in large part the high prevalence of infections, including respiratory tract infections in older persons. Poor nutritional status in many older persons increases susceptibility to infection and worsens prognosis. Interestingly, there is an association between the amount of saturated fats in the diet and the rate of community-acquired pneumonia. Polyunsaturated fatty acids, particularly omega-3 long chain polyunsaturated fatty acids (ω-3 LC-PUFAs) including eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA), have well-known anti-inflammatory, immunomodulatory, and antimicrobial effects, which may, in theory, be largely induced by PUFAs-derived lipids such as specialized pro-resolving mediators (SPMs). In adults, preliminary results of studies show that ω-3 LC-PUFAs supplementation can lead to SPM generation. SPMs have a crucial role in the resolution of inflammation, a factor relevant to survival from infection independent of the pathogen’s virulence. Moreover, the immune system of older adults appears to be more sensitive to ω-3 PUFAs. This review explores the effects of ω-3 LC-PUFAs, and PUFA bioactive lipid-derived SPMs in respiratory tract infections and the possible relevance of these data to infectious disease outcomes in the older population. The hypothesis that PUFAs have beneficial effects via SPM generation will need to be confirmed by animal experiments and patient-derived data.

This article presents a new system for classifying UK charities’ activities according to their charitable purposes. It also outlines our attempts to use keyword search rules to apply these classifications to the various UK charity registers. The classification results and code, which are made freely available online, help to address the limitations of existing classification schemes in the UK context. Depending on the scheme, these include a lack of detail and coverage of important subsectors, a lack of systematic data collection and limits on the number of classifications per charity. We discuss the pros and cons of different approaches and show that the keyword searching method provides a sufficiently accurate and transparent approach. We also present some preliminary results on how commonly each ‘tag’ is matched against UK charities, as well as exploring how the results compare to existing classifications in the register of charities for England and Wales.

Este artículo presenta avances de investigación etnográfica considerando hitos históricos en la migración transnacional de chilotes desde los años cincuenta hasta los ensamblajes actuales en lugares de la Patagonia chilena y argentina. En particular, se analizan etapas de movilidad vinculadas al auge económico en territorios australes, destacando sectores de inserción laboral en ambos lados de la frontera. Los resultados preliminares muestran las conexiones culturales reservadas a lugares de origen y residencia a través de la formación de comunidades, circulación de mercancías, extensión de significados y nuevas trayectorias migratorias interregionales. La plataforma metodológica corresponde a etnografías en movimiento derivadas de acercamientos circunstanciales en diferentes localidades de Chiloé y la Patagonia, entre diciembre de 2015 y mayo de 2017. Las reflexiones en este trabajo hacen un aporte a los estudios sobre movilidades humanas en el sur de Chile analizadas desde perspectivas multilocales, que permiten localizar continuidades culturales en la migración vivida.

Objectives The purpose of this study is to develop a performance-based online assessment tool to measure the level of digital literacy of primary school students. Methods To achieve this, test items were developed based on several scenarios that reflected the context of schools, families, and communities that primary school students encounter in their daily lives, and an online as-sessment system was developed in the form of several sub-tasks being connected to perform one integrated task. The developed assessment tool consisted of 4 test modules and a total of 28 sub-task items. A preliminary test was conducted on 462 primary school students to verify the reliability and validity of the developed online as-sessment system. Results As a result of analyzing the preliminary test results, the test reliability was found to be good. As a result of correlation analysis with the multiple-choice assessment tool, it was found to be distinguished from the exist-ing tool as a performance-based assessment tool. In addition, as a result of item analysis, the overall discrim-ination and difficulty level was found to be at an appropriate level except for a few items. Conclusions This study is significant in that it developed a performance-based online assessment tool beyond self-reporting or knowledge-based multiple-choice assessment, and provided primary data for future research on measuring students’ digital literacy level using a performance-based online assessment tool based on the pre-liminary test results.

Type 2 diabetes (DM) is a common comorbidity associated with cardiovascular disease, especially when poor glucose control is present. Extracardiac microcirculatory complications prevalence is well documented, however coronary microcirculatory dysfunction (CMD) seem to be underreported in this group. The present study analyzed coronary physiology measurements (coronary flow reserve [CFR], index of microcirculatory resistance [IMR], resistance reserve ratio [RRR]) in 47 diabetic patients (21 subjects with poor glycemia control defined as fasting glucose levels > 7.2 mmol/L and 26 with normal fasting glucose), and compared to 54 non-diabetic controls, who had undergone coronary angiography due to symptoms of chronic coronary syndrome. The median age of patients was 65.5 [59.0; 73.0] years old, 74% male, similar in terms of cardiovascular risk factors and prior myocardial infarction. Insulin was used by 19% of diabetic patients with poor glucose control and by 15% of those with DM and low fasting glucose. Prevalence of CMD was 38% in poor glycemia control patients, 27% in DM-patients with proper glucose control and 31% of non-diabetics. Median CFR values were the lowest in poor DM control patients compared to both, normal fasting glucose (1.75 [1.37; 2.32] vs. 2.30 [1.75; 2.85], p = 0.026) and to non-diabetics (1.75 [1.37; 2.32] vs. 2.15 [1.50; 2.95], p = 0.045). Levels of IMR, RRR and MRR did not differ significantly between compared groups (p > 0.05 for all comparisons). Poor glycemia control in type 2 DM might be associated with a higher prevalence of CMD driven by decreased coronary flow reserve, however, further research in larger groups of patients should be performed to confirm this observation.

This research study evaluated the suitability of controlled-release urea (CRU) as an alternate nitrogen (N) fertilizer source to conventional soluble urea (U) for tomato production under a humid, warm climate in coastal plain soils. Tomatoes are typically produced on raised plastic-mulched beds, where U is fertigated through multiple applications. On the other hand, CRU is applied once at planting, incorporated into soil before the raised beds are covered with plastic mulch. N source and management will likely impact tomato yield, N use efficiency (NUE), and apparent recovery of N fertilizer (APR). A 2-year field study was conducted on fall and spring tomato crops in north Florida to determine the crop N requirement and NUE in tomatoes (var. HM 1823) grown in sandy soils under a plastic-mulched bed system. In addition to a no N fertilizer treatment, three urea N sources [one soluble source and two polymer-coated CRU sources with different N release durations of 60 (CRU-60) and 75 (CRU-75) days] were applied at three N rates (140, 168, and 224 kg⋅ha −1 ). Across all N sources and N rates, fall yields were at least 20% higher than spring seasons. At the 140 kg⋅ha −1 N rate, APR and NUE were improved, especially when U was applied in fall tomato, whereas preplant CRUs improved N efficiency in spring tomato. Based on the lower APR values found in spring production seasons (0% to 16%) when compared with fall (57.1% to 72.6%), it can be concluded that residual soil N was an important source for tomatoes. In addition, the mean whole-plant N accumulation of tomato was 102.5 kg⋅ha −1 , further indicating that reducing the N rate closer to crop N demand would greatly improve conventional vegetable production systems on sandy soils in north Florida. In conclusion, polymer-coated CRU and fertigation U applications were able to supply the N requirement of spring and fall tomato at a 38% reduction of the recommended N rate for tomato in Florida (224 kg⋅ha −1 ). Preliminary results show that adoption of CRU fertilizers can be considered a low-risk alternative N source for tomato production and the ease of applying CRU once during the bed preparation period for tomato may be an additional incentive.

INTRODUCTION: Chronic pain is a prevalent issue that may affect up to 34% of US adults, and spinal cord stimulation (SCS) is a promising therapy. However, SCS device selection remains a challenge because there are currently no objective biomarkers to evaluate chronic pain, or to predict which patients will be responders. METHODS: Intraoperative EEG signals were recorded in 24 chronic pain patients (14 women) during permanent SCS electrode placement surgery. Neural responses were captured with respect to tonic (60 Hz/300 µs) and high-frequency (1 kHz/30 µs) SCS paradigms in a randomized manner and correlated to Numeric Rating Scale (NRS) scores. All data were analyzed offline in MATLAB and SPSS v28.0.1.1. RESULTS: Our analyses for the main effects demonstrated a significant difference between cortical regions (F(2.88,57.7) = 7.60 , p < 0.001) and a marginal difference between stimulation conditions (F(2,40) = 2.970, p = 0.063). The post hoc analysis for these factors revealed that alpha/theta peak power ratio was significantly different between in central regions (C3-C4) between tonic and HF stimulation (p = 0.006) and temporal regions (T3-T4) between baseline and HF stimulation (p = 0.049). The comparison of NRS scores before and 3 months after surgery indicated a significant improvement in pain intensity (p < 0.001) at the group level. The neural features found to be significantly correlated with preoperative NRS scores in PFC (p = 0.036 and p = 0.025) and temporal regions (p = 0.041 and p = 0.012) under both stimulations. CONCLUSIONS: Our preliminary results support the possibility that different stimulation patterns affect the electrophysiological activity differently in various cortical regions. Such differences might account for the variability in pain suppression in patients with chronic pain treated with SCS. Future work will utilize this dataset to develop a machine learning classifier to support objective device selection strategies.

This study was undertaken to evaluate the degrading potentials of plasmid and non–plasmid borne soil bacterial strains on Bonny light crude oil. Enrichment technique, turbidometric test, plasmid curing test as well as gas chromatographic flame ionization detection technique was adopted for isolating and evaluating the oil degrading capabilities of the selected bacterial strains. The preliminary physicochemical results revealed that pH was recorded slightly neutral, higher conductivity (0.41 to 0.44 μS/cm), higher organic carbon (2.32 to 4.34 %) but lower nitrogen and phosphorus contents (0.27 % and 10.11 kg) as well as lower water holding capacity was noted, respectively. The results indicated that 22 out of the 60 isolated bacterial strains had high crude oil degrading potentials (A600nm > 0.3). The result further indicated that bacterial strains belong to various species which are Bacillus cereus C12, Pseudomonas aeruginosa KAVK01, Bacillus licheniformis 126, Ochrobacterium intermedium E85b, Bacillus subtillis SDDlas, Bacillus subtillis LK4.5, Enterobacter cloacae GEBRI III and Bacillus cereus So24. Plasmid borne P. aeruginosa strain KAVK01 was the best degrader with 88 % remediation efficiency within the period while the plasmid cured P. aeruginosa strain KAVK01 had 65 % degradation with the order of n – alkane hydrocarbon degradation: (n-C8 - n-C17) > (n-C18 - n-C25) > (n-C26 - n-C32). The data obtained from the current study could help in the selection of bacterial species, most especially plasmid borne bacteria that can be employed in the restoration of oil contaminated soil ecosystem in the Niger Delta region of Nigeria.

Subarachnoid hemorrhage (SAH) is a neurological emergency that can lead to fatal outcomes. It occurs when bleeding happens in the subarachnoid space, a small gap between the arachnoid and pia mater. This condition results from the rupture of diseased or damaged blood vessels at the brain's base or surface. This study combined various omics approaches with Mendelian randomization analysis, including MR-IVW, MR Egger, MR weight median, and MR weight mode, to generate preliminary results. It also employed reverse Mendelian randomization, treating SAH as the exposure. Finally, a meta-analysis was conducted to summarize these findings. The study found positive correlations between SAH and both GBPA-Pyridoxal 5 phosphate biosynthesis I (OR=1.48, 95% CI, 1.04-2.12) and GBPA-glucose biosynthesis I (OR=0.68, 95% CI, 0.52-0.90). Increased levels of urokinase-type plasma activator were also associated with SAH (OR=1.17, 95% CI, 1.04-1.32). Associations were observed with SAH for CD80 on CD62L+ plasmacytoid dendritic cells, CD80 on plasmacytoid dendritic cells, CD123 on CD62L+ plasmacytoid dendritic cells, and SSC-A on plasmacytoid dendritic cells. This study, through Mendelian randomization and meta-analysis, established links between SAH and four inflammatory cells, one inflammatory protein, and two gut microbiota-related pathways. These findings suggest potential treatment targets for SAH, highlighting the importance of modulating gut microbiota and utilizing anti-inflammatory drugs in its management.

Erectile dysfunction (ED) is a common clinical condition that mainly affects men aged over 40 years. Various causes contribute to the progression of ED, including pelvic nerve injury, diabetes, metabolic syndrome, age, Peyronie's disease, smoking, and psychological disorders. Current treatments for ED are limited to symptom relief and do not address the root cause. Stem cells, with their powerful ability to proliferate and differentiate, are a promising approach for the treatment of male ED and are gradually gaining widespread attention. Current uses for treating ED have been studied primarily in experimental animals, with most studies observing improvements in erectile quality as well as improvements in erectile tissue. However, research on stem cell therapy for human ED is still limited. This article summarizes the recent literature on basic stem cell research on ED, including cavernous nerve injury, aging, diabetes, and sclerosing penile disease, and describes mechanisms of action and therapeutic effects of various stem cell therapies in experimental animals. Stem cells are also believed to interact with host tissue in a paracrine manner, and improved function can be supported through both implantation and paracrine factors. To date, stem cells have shown some preliminary promising results in animal and human models of ED.

Abstract Introduction: Pancreatic cancer accounts for 3% of cancer cases and 7% of cancer deaths in the United States. It is currently in the third position with respect to cancer-related deaths, and it is expected to move to second place as of 2040. This is mainly due to its diagnosis in the later stage. If detected in the first or second stage surgery can be performed thus increasing the patient’s survival rate. The current methods of diagnosis cannot do early stage or asymptomatic detection. So, detecting cancer-specific biomarkers can aid in the prognosis. Serum protein-based biomarkers carbohydrate antigen CA242, CA19-9, and carcinoembryonic antigen CEA are specific to pancreatic cancer. Thus, in this preliminary study, we aim to develop a nanoengineered electrochemical biosensor combined with machine learning to detect pancreatic cancer-specific biomarkers CA242, CA19-9, and CEA. Methodology: Nanoengineering the biosensor: The gold working electrode of the gold- biosensor (DRP-250AT) was coated with graphene oxide nano colloidal solution and kept in UV overnight for the graphene oxide nanosheet to crosslink with the working electrode. Detection of biomarkers using an electrochemical biosensor: First, a Crosslinker (DSP) was added to ethanol cleaned biosensor to bind the analytes. Following that antibody specific to each biomarker were added to the biosensors. The addition of TBS superblock prevented non-specific binding. Then different concentrations of biomarkers were added, and the corresponding sensor was subjected to various electrochemical analyses such as electrochemical impedance spectroscopy and voltammetry. SEM-EDAX analysis: The antigen-antibody binding on the biosensor's surface was confirmed. Automation and machine learning: Python code was developed to automate the analysis process and machine learning models (support vector machine and neural network) were used to classify the concentrations into various risk levels. The sensitivity of the developed tool was high when compared with conventional methods like ELISA and confocal microscopy. Results: From the electrochemical studies we found that with increasing concentration of biomarkers, there was a trend in output parameters: capacitance, resistance, impedance and area under the curve. By analyzing this trend, the concentrations of biomarkers can be detected. Using this data as input the machine learning model (accuracy greater than 80%) classified the concentrations into risk levels (normal, low risk, and high risk). Significance: Nanoengineering with graphene oxide nanosheets enhances the sensitivity of electrochemical biosensors. Automation and machine learning models help in the analysis of large datasets produced by this sensor. Overall, this device aids in the prognosis of pancreatic cancer. Our preliminary results are encouraging but more thorough research is required to make this diagnostic tool a working application. Citation Format: Meenal Karunanidhi, Hemalatha Kanniyappan, Edith Zhan, Ruth Mathew, Yani Sun, Junyi Wu, Yan Yan, Gnanasekar Munirathinum, Mathew T. Mathew. PancreaAlert: Intelligent nanoengineered biosensor for pancreatic cancer [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 1 (Regular Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(6_Suppl):Abstract nr 7289.

Abstract Human leukocyte antigen-G (HLA-G) suppresses lymphoid and myeloid immune systems by binding ILT2 and ILT4 respectively and activating ITIM signaling. HLA-G is abundantly expressed in placental cytotrophoblasts to block fetal rejection. HLA-G is not expressed in most normal cells but is derepressed in in about 50% of malignancies. We engineered ILT2 and ILT4 to produce activating signals as Chimeric ILT Receptors or CIR. Preliminary results indicated robust killing of Acute Myeloid Leukemia (AML) cells by Natural Killer (NK) cells expressing either ILT2 or ILT4 CIRs. Here, we evaluated the effect of alteration of activating domains in the CIR constructs to produce signals that mimic the effect of IL-18 signaling in CIR-NK cells to enhance cytotoxicity, NK cell growth and persistence. Further, HLA-G expression and CIR-NK cell targeting of primary human cell types were rigorously screened. Activated NK cells derived from peripheral blood (2 to 5 donors) were transduced with γ-retroviruses directing expression of CIR proteins (CIR.X.Y or CIR.Y.X) where X stimulates cytotoxicity through CD3ζ, DAP10 or DAP12, and Y directs coactivation through 4-1BB, fusion of the MyD88 death domain or recruitment of endogenous MyD88 with receptor-derived TIR domains and soluble IL-15. CIR-NK cells were cocultured with GFPffluc-expressing AML and solid tumor target cell lines or normal primary human cells. NK cell proliferation and cytotoxicity of CIR-NK cells was monitored by Incucyte microscopy and supernatants were analyzed for cytokine release by ELISA. At low E:T (1:20 - 1:40) in 7-day cocultures, mock-transduced NK cells displayed innate killing activity against HLA-G+ Molm13 and Kasumi1 AML cells that was augmented by CIR constructs containing direct fusions of MyD88 and DAP10 or DAP12 (mock = 2.06E7 ± 4.53E6 vs. CIR-ILT4.MyD88.DAP10 = 1.03E7 ± 5.46E6) with 7-fold elevation of IFN-γ production. CIR constructs that recruited endogenous MyD88 signaling through the TLR2 TIR domain (4-1BB.DAP10.TLR2) also exhibited enhanced anti-HLA-G activity (9.13E6 ± 5.33E6). Against HLA-G+ HT-1376 bladder cancer cells (E:T = 1:10-1:20), CIR-NK cells also displayed enhanced tumor cell killing with enhanced NK cell growth. Conversely, CIR-enhanced killing was not observed against HLA-G− HCT-116 colorectal cancer cells. The persistence of CIR-NK cell potency after 4 weeks of expansion varied markedly with different activation domains employed. When screened against primary human cells (cardiomyocytes, hepatocytes, hepatic endothelial cells, corneal, colon and lung epithelial cells), no CIR-specific targeting was observed at high E:T ratios (1:1 and 1:5). In conclusion, CIR-NK cells exhibit potent and specific anti-tumor activity against HLA-G+ solid and leukemia cells. Alteration of CIR-NK cell intracellular signaling can optimize the potency and persistence of NK cell anti-tumor activity. Citation Format: MyLinh Duong, Jihyun Park, Raphel Ognar, Simon Wain-Hobson, Henri Bayle. Novel activation domains coupled to chimeric ILT receptors (CIR) enhance NK cell targeting of HLA-G+leukemic and solid tumor cells [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 1 (Regular Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(6_Suppl):Abstract nr 1338.

Abstract Prostate cancer is the most common cancer and the second leading cause of cancer death among men in the United States. There is an estimated 10% to 50% of cases progress to metastatic castration resistant prostate cancer (mCRPC) state within 3 years of diagnosis. mCPRC remains lethal despite therapeutic advances. There is approximately 20% of mCRPC patients present somatic DNA damage repair (DDR) gene mutations. Ceralasertib, formerly known as AZD6738, is a potent and selective orally bioavailable inhibitor of the ataxia tenlangiectasia and Rad3-related (ATR) kinase, which is involved in DNA repair in response to DNA damage and replication stress. Preclinical studies have demonstrated ATRi sensitizing alterations in DNA damage response (DDR) genes. Ceralasertib’s antitumor activity as a monotherapy in treating prostate cancer is moderate. Thus, we combined ceralasertib with imipridones (ONC201 and ONC206), which target mitochondrial caseinolytic protease P (ClpP) and the integrated stress response, resulting in enhanced antitumor efficacy in vitro. Prior data have demonstrated sensitivity of 4 prostate cancer lines to ceralasertib and imipridones monotherapies, synergistic activities with the combination treatments, and immune enhancement effects with the combination treatments when co-cultured with NK92MI cell line. We proceeded to a short term in-vivo study validating the combination treatment efficacy. Preliminary results include cytokine profiling using the Luminex 200 technology to understand treatment induced changes in the tumor microenvironment (TME) from both in vitro and in vivo studies. Our results guide novel clinical trials for effective clinical responses in mCPRC patients. Citation Format: Yutong Linda Xia, Leiqing Zhang, Maryam Ghandali, Maximilian P. Schwermann, Wafik El-Deiry. The anti-tumor efficacy and immune effects of combining of ceralasertib, an oral ATR kinase inhibitor, with imipridones, in prostate cancer treatment in vitro and in vivo [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 1 (Regular Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(6_Suppl):Abstract nr 5559.

Alzheimer's disease (AD), referring to a gradual deterioration in cognitive function, including memory loss and impaired thinking skills, has emerged as a substantial worldwide challenge with profound social and economic implications. As the prevalence of AD continues to rise and the population ages, there is an imperative demand for innovative imaging techniques to help improve our understanding of these complex conditions. Photoacoustic (PA) imaging forms a hybrid imaging modality by integrating the high-contrast of optical imaging and deep-penetration of ultrasound imaging. PA imaging enables the visualization and characterization of tissue structures and multifunctional information at high resolution and, has demonstrated promising preliminary results in the study and diagnosis of AD. This review endeavors to offer a thorough overview of the current applications and potential of PA imaging on AD diagnosis and treatment. Firstly, the structural, functional, molecular parameter changes associated with AD-related brain imaging captured by PA imaging will be summarized, shaping the diagnostic standpoint of this review. Then, the therapeutic methods aimed at AD is discussed further. Lastly, the potential solutions and clinical applications to expand the extent of PA imaging into deeper AD scenarios is proposed. While certain aspects might not be fully covered, this mini-review provides valuable insights into AD diagnosis and treatment through the utilization of innovative tissue photothermal effects. We hope that it will spark further exploration in this field, fostering improved and earlier theranostics for AD.

One of the important aspects is the interaction of plasma with the surface of a material, especially in the conditions of a fusion facility. The current work presents the preliminary results of the study of tungsten surface structure modification under helium plasma irradiation. A small-sized linear simulator KAZ-PSI with a plasma-beam setup was designed and assembled, where helium was used as a working gas. The main elements of the linear plasma simulator are an electron beam gun with a LaB6 cathode, a plasma-beam discharge chamber, an interaction chamber, a target device, and an electromagnetic system consisting of electromagnetic coils. It was revealed that under irradiation on the surface of the samples there is a relief with defective structure consisting of chaotically arranged ledges and pits of various shapes with average size (100‒600) nm and pore sizes (0.1‒1.5) μm with visible areas of flaking and sputtering. It was found that when the negative potential on the target is varied by –500V/–1000V/–1500V, the formation of dislocation with chaotic and cellular structure of tungsten with an average grain size of (1‒25) μm is observed; it was revealed that the total values of elastic and plastic components of deformation across the tungsten grain differ from each other by about 2.5 times.