Increased Survival Rate Research Articles

Unmet supportive care needs of patients with colorectal cancer based on survival stage: A scoping review.

Colorectal cancer (CRC) has emerged as one of the most common cancers, with increasing survival rates globally. As patients with CRC experience diverse treatment effects corresponding to different survival stages, understanding their unmet needs based on the survival stage is critical to tailor supportive care with limited medical resources. This study aimed to understand the unmet needs of patients with CRC across survival stages. This scoping review followed the 5-stage framework established by Arksey and O'Malley. Five online databases were searched with narrative synthesis performed after data extraction. Fifteen studies were identified for this review, with 12 focusing on the acute survival stage and three reporting on the extended survival stage. Ten studies used validated scales to assess unmet needs, with the Supportive Care Needs Survey being the most common scale. Unmet needs in patients with CRC demonstrate distinct patterns across survival stages. Most studies reported a higher prevalence of unmet needs during the extended survival stage compared to the acute survival stage. Unmet emotional needs predominate during the acute survival stage, whereas unmet physical needs become most prominent in the extended survival stage. Healthcare providers are encouraged to conduct assessments tailored to the specific survival stage, with particular emphasis on addressing unmet needs during the extended survival stage. The development of standardized scales is recommended to comprehensively assess the unmet needsof patients with CRC.

Interleukin-1 receptor 1 deficiency worsens hepatocellular carcinoma, while gemcitabine treatment alleviates the hepatocellular carcinoma-induced increase in intra-hepatic immune cells.

Primary liver cancer, particularly hepatocellular carcinoma (HCC), represents a substantial global health challenge. Although immune checkpoint inhibitors are effective in HCC treatment, several patients still experience disease progression. Interleukin-1 (IL-1) regulates immunity and inflammation. We investigate the role of IL-1 in HCC development and progression and determine the potential therapeutic impact of gemcitabine in treating HCC. Hydrodynamics-based transfection, employing the sleeping beauty transposase system, delivered surrogate tumor antigens, NRAS (NRAS proto-oncogene, GTPase), ShP53, and SB100 to C57BL/6 mice. A basic HCC mouse model was established. Pathogen-free animals were tested for serum and hepatotoxicity. The HCC prognosis was monitored using alanine aminotransferase and aspartate aminotransferase levels. Liver histology immunohistochemistry and mouse splenocyte/intra-hepatic immune cell flow cytometry were conducted. IL-1β levels in human and mouse serum were assessed. Interleukin-1β levels were elevated in patients with HCC compared with those in non-HCC controls. Hepatic IL-1β levels were higher in HCC mouse models than those in non-HCC mice, suggesting localized hepatic inflammation. IL-1 receptor type 1 (IL-1R1) knockout (IL-1R1-/-) mice exhibited less severe HCC progression than that in wild-type mice, despite the high intra-hepatic IL-1β concentration. IL-1R1-/- mice exhibited increased hepatic levels of myeloid-derived suppressor cells and regulatory T cells, which may exacerbate HCC. Gemcitabine significantly reduced the HCC tumor burden, improved liver conditions, and increased survival rates in HCC mouse models. Gemcitabine reduced the hepatic levels of myeloid-derived suppressor cells and regulatory T cells, potentially alleviating immune suppression in the liver. Targeting IL-1 or combining gemcitabine with immunotherapy is a promising approach for treating advanced-stage HCC.

The impact of Neoporphyra haitanensis dietary supplement on astaxanthin esters and fatty acids accumulation associated with immune promotion in Pacific white shrimp (Litopenaeus vannamei)

To explore and develop effective feed additives for enhancing shrimp cultivation, an 8-week feeding experiment was conducted in Litopenaeus vannamei with dietary supplementation ranging from 0% to 5% Neoporphyra haitanensis. The results indicated that a diet containing 2% N. haitanensis enhanced trypsin activity, as well as the height and width of intestinal villi, leading to improved growth performance of L. vannamei. The specific growth rate (SGR), weight gain rate (WGR) and the ratio of flesh content were increased by 1.1 to 2.0 times, while the hepatosomatic index (HSI) and condition factor (CF) values were 85.6% and 91.5% of those in the control group, respectively. Additionally, the inclusion of 2% N. haitanensis in the diet led to a 1.1-fold increase in the accumulation of fatty acids, particularly DHA and EPA. The diet also exhibited elevated levels of β-carotene, zeaxanthin, α-cryptoxanthin, and β-cryptoxanthin, which correlated with the increased content of carotenoids in the shrimp. The exoskeleton was identified as the primary site for assimilating α−/β-carotenes, free astaxanthin, and its diesters (mainly EPA and DHA chains), accompanied by heightened redness (a*) value. Meanwhile, the muscle tended to accumulate astaxanthin and its monoesters (mainly C16:0 and C18:0 chains) and hepatopancreas had lowest contents of astaxanthin and its diesters (mainly DHA chain). Furthermore, the Toll and IMD immune signal pathways in L. vannamei were activated with 2% N. haitanensis in the die, up-regulating the expression of immune-related genes dorsal, relish and imd, and antibacterial peptides genes crustin, lysozyme, and penaeidin3a. Concurrently, the activities of immune-related enzymes ACP and AKP, as well as antioxidant enzymes CAT, SOD, and GPH-Px, were enhanced, while AST and ALT activities were decreased. In terms of intestinal health, the addition of 2% N haitanensis contributed to the preservation of the intestinal tissue structure and promoted the abundance of beneficial bacteria, while reducing the abundance of Vibrio in L. vannamei. The enhanced immune and antioxidant performance of L. vannamei was demonstrated to prevent intestinal structure damage and increase survival rates, as evidenced by WSSV infection experiments. These results offer valuable insights into the dose-dependent effects of dietary seaweeds in promoting shrimp cultivation.

Specific depletion of myeloid-derived suppressor cells by the chemotherapeutic agent 5-Fluorouracil enhances protective immune response in Paracoccidioidomycosis.

Paracoccidioidomycosis (PCM), a systemic mycosis in Latin America, is regulated by suppressive mechanisms mediated by tolerogenic plasmacytoid-dendritic-cells and regulatory T-cells. Our recent studies revealed that myeloid-derived suppressor cells (MDSCs), are important mediators in PCM. Their suppressive activity on Th1/Th17 immunity was shown to be mediated by inhibitory effect of IL-10, IDO-1 and PD-L1. Studies revealed the chemotherapeutic drug 5-Fluorouracil (5-FU) as a selective MDSC apoptosis-inducing agent, but its in vivo effect on infectious processes remains poorly investigated. MDSCs and other leukocytes were evaluated in the lungs of 5-FU-treated mice after four, six, and eight weeks of P. brasiliensis infection. Disease severity and immunological response were evaluated in MDSCs-depleted. 5-FU treatment caused a significant reduction of pulmonary MDSCs and fungal loads. The specific depletion of MDSCs by 5-FU reduced all pulmonary CD4+ T-cell populations (Th1, Th2, Th17, and Treg) resulting in improved tissue pathology and increased survival rates. Importantly, this reduction was concomitant with increased frequencies of Th1/Th17 cells and the increased levels of Th1/Th2/Th17 cytokines in the lungs and liver of treated mice suggesting an early and efficient protective effect of these cells. Furthermore, the immuneprotection conferred by the specific depletion of MDSCs by 5FU treatment could be reversed by the adoptive transfer of MDSCs. 5-FU treatment depletes lung-MDSCs of P. brasiliensis-infected mice resulting in enhanced immunity. The protective effect of 5-FU treatment in pulmonary PCM suggests that the specific depletion of MDSCs can be viewed as a potential immunotherapeutic tool for PCM.

Population based study on the progress in survival of primarily metastatic lung cancer patients in Germany

Lung cancer is known for its high mortality; many patients already present with metastases at the time of diagnosis. The aim of this study is to assess the impact of new treatment strategies on the survival of primarily metastatic lung cancer patients and to analyze the differences in outcomes between non-small cell lung cancer (NSCLC) and small cell lung cancer (SCLC) patients. Population-based data, provided by the Robert-Koch Institute in Germany, was used and patients diagnosed between 2007 and 2018 were included in the study. We differentiated between NSCLC and SCLC patients and analyzed the survival over time for both sexes separately, using the Kaplan–Meier method. To evaluate survival advantages, we calculated multivariable hazard ratios. In total, 127,723 patients were considered for the study. We observed a moderate increase in survival over time. All patients showed an increased survival rate when undergoing chemotherapy. Minimal to no increase in survival was shown in NSCLC patients when receiving radiotherapy, whereas SCLC patients’ survival time did benefit from it. NSCLC patients receiving immunotherapy showed an increase in survival as well. It can be concluded that advancements in radiotherapy, the application of chemotherapy, and the introduction of immunotherapies lead to an increased survival time of both NSCLC and SCLC primarily metastatic lung cancer patients.

FLASH proton reirradiation, with or without hypofractionation, mitigates chronic toxicity in the normal murine intestine, skin, and bone.

The normal tissue sparing afforded by FLASH radiotherapy (RT) is being intensely investigated for potential clinical translation. Here, we studied the effects of FLASH proton RT (F-PRT) in the reirradiation setting, with or without hypofractionation. Chronic toxicities in three murine models of normal tissue toxicity including the intestine, skin, and bone were investigated. In studies of the intestine, single-dose irradiation was performed with 12 Gy of Standard proton RT (S-PRT), followed by a second dose of 12 Gy of F-PRT or S-PRT. Additionally, a hypofractionation scheme was applied in the reirradiation setting (3 x 6.4 Gy of F-PRT or S-PRT, given every 48 hrs). In studies of skin/bone of the murine leg, 15 Gy of S-PRT was followed by hypofractionated reirradiation with F-PRT or S-PRT (3 x 11 Gy). Compared to reirradiation with S-PRT, F-PRT reduced intestinal fibrosis and collagen deposition in the reirradiation setting and significantly increased survival rate, demonstrating its protective effects on intestinal tissues. In previously irradiated leg tissues, reirradiation with hypofractionated F-PRT created transient dermatitis that fully resolved in contrast to reirradiation with hypofractionated S-PRT. Lymphedema was also alleviated after a second course of radiation with F-PRT, along with significant reductions in the accumulation of fibrous connective tissue in the skin compared to mice reirradiated with S-PRT. The delivery of a second course of fractionated S-PRT induced tibial fractures in 83.3% of the mice, whereas only 20% of mice reirradiated with F-PRT presented with fractures. These studies provide the first evidence of the sparing effects of F-PRT, in the setting of hypofractionated reirradiation. The results support FLASH as highly relevant to the reirradiation regimen where it exhibits significant potential to minimize chronic complications for patients undergoing RT.

A small molecule compound targeting hemagglutinin inhibits influenza A virus and exhibits broad-spectrum antiviral activity.

Influenza A virus (IAV) is a widespread pathogen that poses a significant threat to human health, causing pandemics with high mortality and pathogenicity. Given the emergence of increasingly drug-resistant strains of IAV, currently available antiviral drugs have been reported to be inadequate to meet clinical demands. Therefore, continuous exploration of safe, effective and broad-spectrum antiviral medications is urgently required. Here, we found that the small molecule compound J1 exhibited low toxicity both in vitro and in vivo. Moreover, J1 exhibits broad-spectrum antiviral activity against enveloped viruses, including IAV, respiratory syncytial virus (RSV), severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), human coronavirus OC43 (HCoV-OC43), herpes simplex virus type 1 (HSV-1) and HSV-2. In this study, we explored the inhibitory effects and mechanism of action of J1 on IAV in vivo and in vitro. The results showed that J1 inhibited infection by IAV strains, including H1N1, H7N9, H5N1 and H3N2, as well as by oseltamivir-resistant strains. Mechanistic studies have shown that J1 blocks IAV infection mainly through specific interactions with the influenza virus hemagglutinin HA2 subunit, thereby blocking membrane fusion. BALB/c mice were used to establish a model of acute lung injury (ALI) induced by IAV. Treatment with J1 increased survival rates and reduced viral titers, lung index and lung inflammatory damage in virus-infected mice. In conclusion, J1 possesses significant anti-IAV effects in vitro and in vivo, providing insights into the development of broad-spectrum antivirals against future pandemics.

Late effects of Wilms' tumor treatment.

Wilms' tumor (WT) is the most frequent renal tumor in childhood. Therapeutic management progression has increased survival rates, and as a result, long-term adverse effects. A descriptive retrospective study of a case series from 1977 to 2023 was carried out. The characteristics of the treatments received and the adverse effects listed on medical records were analyzed via phone surveys. 50 patients (25 boys-25 girls) with a mean age of 3.6 years (3 months-11years) at diagnosis were included. Most of them (94%) were treated according to the protocol established by the European standards of pediatric oncology, which are characterized by the use of neoadjuvant chemotherapy. In one patient, the American treatment scheme was followed. The most common drugs used were vincristine and actinomycin D (78%). Only 12 patients (28%) received anthracyclines. Unilateral nephrectomy was the most frequent surgical technique (84%). Renal disorders were the most common (46%). However, the occurrence of second neoplasias (9%) and reproductive disorders (8% between boys and girls) had a greater impact on patients' quality of life. Multiple - cardiac (23%), endocrine (26%), and pulmonary (15%) - disorders associated with the treatments received were reported. WT treatment has an impact on health. Adequate and rigorous surgery, close follow-up, and limiting chemotherapy doses and radiation exposure can minimize long-term sequels.

LILRB4 knockdown inhibits aortic dissection development by regulating pyroptosis and the JAK2/STAT3 signaling pathway

Aortic dissection (AD) is a life-threatening condition with a high mortality rate and without effective pharmacological therapies. Our previous study illustrated that leukocyte immunoglobulin-like receptor B4 (LILRB4) knockdown promoted the contractile phenotypic switch and apoptosis of AD cells. This study aimed to further investigate the role of LILRB4 in animal models of AD and elucidate its underlying molecular mechanisms. Animal models of AD were established using 0.1% beta-aminopropionitrile and angiotensin II and an in vitro model was developed using platelet-derived growth factor BB (PDGF-BB). The effects of LILRB4 knockdown on histopathological changes, pyroptosis, phenotype transition, extracellular matrix (ECM), and Janus kinase 2 (JAK2)/signal transducers and activators of transcription 3 (STAT3) pathways were assessed using a series of in vivo and in vitro assays. The effects of the JAK2 inhibitor AG490 on AD cell function, phenotypic transition, and ECM were explored. LILRB4 was highly expressed in AD and its knockdown increased survival rate, reduced AD incidence, and alleviated histopathological changes in the AD mouse model. Furthermore, LILRB4 knockdown promoted contractile phenotype switch, stabilized the ECM, and inhibited pyroptosis. Mechanistically, LILRB4 knockdown inhibited the JAK2/STAT3 signaling pathway. JAK2 inhibitor AG490 inhibited cell viability and migration, enhanced apoptosis, induced G0/G1 cell cycle arrest, and suppressed S-phase progression in PDGF-BB-stimulated human aortic smooth muscle cells. LILRB4 knockdown suppresses AD development by inhibiting pyroptosis and the JAK2/STAT3 signaling pathway.

In Vitro Generation of Haploid Germ Cells from Human XY and XXY Immature Testes in a 3D Organoid System.

Increasing survival rates of children following cancer treatment have resulted in a significant population of adult survivors with the common side effect of infertility. Additionally, the availability of genetic testing has identified Klinefelter syndrome (classic 47,XXY) as the cause of future male infertility for a significant number of prepubertal patients. This study explores new spermatogonia stem cell (SSC)-based fertility therapies to meet the needs of these patients. Testicular cells were isolated from cryopreserved human testes tissue stored from XY and XXY prepubertal patients and propagated in a two-dimensional culture. Cells were then incorporated into a 3D human testicular organoid (HTO) system. During a 3-week culture period, HTOs maintained their structure, viability, and metabolic activity. Cell-specific PCR and flow cytometry markers identified undifferentiated spermatogonia, Sertoli, Leydig, and peritubular cells within the HTOs. Testosterone was produced by the HTOs both with and without hCG stimulation. Upregulation of postmeiotic germ cell markers was detected after 23 days in culture. Fluorescence in situ hybridization (FISH) of chromosomes X, Y, and 18 identified haploid cells in the in vitro differentiated HTOs. Thus, 3D HTOs were successfully generated from isolated immature human testicular cells from both euploid (XY) and Klinefelter (XXY) patients, supporting androgen production and germ cell differentiation in vitro.

The role of radiotherapy in multimodal treatment of non-rhabdomyosarcoma soft tissue sarcomas in children: A real life report from a tertiary center.

The current treatment of pediatric non-rhabdomyosarcoma soft tissue sarcomas (NRSTS) is a multimodal risk-based approach. Today, smaller fields and lower doses of radiotherapy (RT) have become standard. In this study, it was aimed to evaluate the treatment outcomes and toxicity profile in children with NRSTS that received RT as a part of multimodal therapy. Twenty-nine patients with pediatric NRSTS treated with neoadjuvant or adjuvant RT between 1998 and 2022 were evaluated retrospectively. Kaplan-Meier method was used for survival analyses. Median follow-up was 36 months (range, 6-291 months). The median neoadjuvant and adjuvant RT doses were 50 Gy (range, 45-66 Gy) and 54 Gy (45-66 Gy), respectively. During follow-up, six (21%) patients developed a local recurrence and 10 (35%) had distant metastasis. The 5-year local control, overall survival (OS), local recurrence-free survival, and distant metastasis-free survival rate was 79%, 67%, 59%, and 61%, respectively. In multivariate analysis, a ≤5-cm tumor, gross tumor resection, Children's Oncology Group (COG) low-risk group, and absence of neoadjuvant chemotherapy were independent favorable prognostic factors for OS. Severe (≥ grade 3) late toxicity was observed in 6 (20%) patients. RT is a crucial component in the multimodal risk-based treatment approach for pediatric NRSTS. However, late toxicity rates are still high and should be improved. Patients with a ≤5-cm tumor, COG low-risk group and treated with gross tumor resection have increased survival rates.

Genotyping and Antiretroviral Drug Resistance Mutations among HIV Patients in Southern Santa Catarina, Brazil.

Therapeutic measures have been successful in increasing survival rates and quality of life of HIV/AIDS-infected people. However, some people fail to respond to antiretroviral therapy (HAART) because of viral resistance-associated mutations. To identify virus genotype and the presence of mutations that alter the susceptibility to HAART, and factors associated with the occurrence of these mutations. A cross-sectional study was conducted on adults living with HIV attending a specialized outpatient clinic in southern Santa Catarina, Brazil. The participants were interviewed and had blood samples collected for analysis. Those with detectable viral load were genotyped. Out of the 629 patients recruited, 127 subjects were included due to having a detectable viral load. The most common mutations were M184V and K103N. HIV-1 subtype C was the most prevalent strain. Resistance to HAART was associated with modification in the treatment regimen (p <0.001). This study concluded that the circulating subtype virus was subtype C and that the mutations K103N and M184V were the most prevalent strains in southern Santa Catarina, Brazil.

The Role of Early Diagnosis and Intervention in Improving Outcomes for Lung Cancer

Introduction : For lung cancer patients, early diagnosis and treatments are essential to battering outcomes. The objective of this world is to compare early diagnosis vs late diagnosis in terms of overall survival ,progression _free survival, quality of life and adverse events associated to treatment. Methodology: A Prospective cohort trial of seventy_ eight lung cancer patients was Conducted at Hayatabad Medical Complex in Peshawar from December 2021 to March 2024. 39 patients had early diagnosis (n=39) while 39 received late diagnosis(n=39) . Low_ dose Computed Tomography (DCT) screening and prompt symptom presentation lead to early diagnosis; incidental or symptomatic results were the basis for late diagnosis. Overall Survival(OS) , progression_ free survival (PFS), quality of life(QoL) , and frequency of serious adverse events associated to therapy were the outcomes. Results: At a median 'OS of 38 months compared to 14 months in the late diagnosis group (p&lt;0.001) and median PFS of 34 months compared to 10 months(p&lt;0.001), the early diagnosis group showed noticeably superior results. At 12 months, 'the early diagnosis group had a better QoL scores' a mean global health status of 75 compared to 55(p&lt;0.01). Early diagnosis group (18%) had a lower frequency of serious adverse effects than did the late diagnosis group(45%). Conclusion: In patients with lung cancer, early detection and intervention greatly increases survival rates, prolong intervals without progression, improves quality of life, and lower serious side effects associated to therapy. The results emphasized the need of early diagnosis techniques and efficient screening programs in the treatment of lung cancer. Keywords: lung Cancer, early diagnosis, low dose computed tomography, overall survival, progression free survival, quality of life, treatment related adverse events

ENHANCE SKIN CANCER DEEP LEARNING-BASED CATEGORIZATION: A THOROUGH EXAMINATION AND COMPARATIVE STUDY

Abstract: One of the most prevalent types of cancer in the world is skin cancer, which includes melanoma, squamous cell carcinoma, and basal cell carcinoma. While increasing survival rates requires early discovery and treatment, conventional diagnostic techniques frequently have subjectivity and inconsistent results. The purpose of this study is to better understand how deep learning techniques, namely convolutional neural networks (CNNs), might improve the detection of skin cancer. Using the ISIC dataset, eight advanced models—DenseNet121, InceptionV3, ResNet50V2, VGG16, VGG19, InceptionResNetV2, Xception, and CNN—were trained and verified to categorize different types of skin lesions. The outcomes highlight the superior accuracy that models like as Xception and InceptionV3 can accomplish, highlighting their potential for accurate and timely detection. This investigation assesses how well different deep learning models diagnose different skin diseases. Models like Densenet121, InceptionV3, and VGG16 are compared based on metrics like accuracy, recall, precision, and F1-score. When it comes to multi-classification, InceptionResNetV2 and VGG16 stand out as the best performers with 0.9547 accuracy, while Custom CNN performs the worst with 0.8040. A thorough comparison of the accuracy, precision, recall, and F1-score performance indicators identifies the unique advantages and disadvantages of each model. This study demonstrates how artificial intelligence (AI) is revolutionizing medical imaging by offering a reliable, unbiased, and highly accurate method for detecting skin cancer. The integration of deep learning models into clinical practice is made possible by these discoveries, which might enhance patient outcomes and diagnostic accuracy in dermatology. IndexTerms – Python, Machine Learning, Deep Learning, Skin Cancer, Deep Learning Algorithms, Medical Imaging, Neural Network Models.

Maresin 1 alleviates neuroinflammation and cognitive decline in a mouse model of cecal ligation and puncture.

Inflammation in the central nervous system plays a crucial role in the occurrence and development of sepsis-associated encephalopathy. This study aims to explore the effects of maresin 1 (MaR1), an anti-inflammatory and pro-resolving lipid mediator, on sepsis-induced neuroinflammation and cognitive impairment. Mice were randomly assigned to 4 groups: A sham group (sham operation+vehicle), a cecal ligation and puncture (CLP) group (CLP operation+vehicle), a MaR1-LD group (CLP operation+1 ng MaR1), and a MaR1-HD group (CLP operation+10 ng MaR1). MaR1 or vehicle was intraperitoneally administered starting 1 h before CLP operation, then every other day for 7 days. Survival rates were monitored, and serum inflammatory cytokines [tumor necrosis factor alpha (TNF-α), interleukin (IL)-1β, and IL-6] were measured 24 h after operation using enzyme-linked immunosorbent assay (ELISA). Cognitive function was assessed 7 days after operation using the Morris water maze (MWM) test and novel object recognition (NOR) task. The mRNA expression of TNF-α, IL-1β, IL-6, inducible nitric oxide synthase (iNOS), IL-4, IL-10, and arginase 1 (Arg1) in cortical and hippocampal tissues was determined by real-time reverse transcription PCR (RT-PCR). Western blotting was used to determine the protein expression of iNOS, Arg1, signal transducer and activator of transcription 6 (STAT6), peroxisome proliferator-activated receptor gamma (PPARγ), and phosphorylated STAT6 (p-STAT6) in hippocampal tissue. Microglia activation was visualized via immunofluorescence. Mice were also treated with the PPARγ antagonist GW9662 to confirm the involvement of this pathway in MaR1's effects. CLP increased serum levels of TNF-α, IL-1β, and IL-6, and reduced body weight and survival rates (all P<0.05). Both 1 ng and 10 ng doses of MaR1 significantly reduced serum TNF-α, IL-1β, and IL-6 levels, improved body weight, and increased survival rates (all P<0.05). No significant difference in efficacy was observed between the 2 doses (all P>0.05). MWM test and NOR task indicated that CLP impaired spatial learning, which MaR1 mitigated. However, GW9662 partially reversed MaR1's protective effects. Real-time RT-PCR results demonstrated that, compared to the sham group, mRNA expression of TNF-α, IL-1β, and iNOS significantly increased in hippocampal tissues following CLP (all P<0.05), while IL-4, IL-10, and Arg1 showed a slight decrease, though the differences were not statistically significant (all P>0.05). Compared to the CLP group, both 1 ng and 10 ng MaR1 decreased TNF-α, IL-1β, and iNOS mRNA expression in hippocampal tissues and increased IL-4, IL-10, and Arg1 mRNA expression (all P<0.05). Immunofluorescence results indicated a significant increase in Iba1-positive microglia in the hippocampus after CLP compared to the sham group (P<0.05). Administration of 1 ng and 10 ng MaR1 reduced the percentage area of Iba1-positive cells in the hippocampus compared to the CLP group (both P<0.05). Western blotting results showed that, compared to the CLP group, both 1 ng and 10 ng MaR1 down-regulated the iNOS expression, while up-regulated the expression of Arg1, PPARγ, and p-STAT6 (all P<0.05). However, the inclusion of GW9662 counteracted the MaR1-induced upregulation of Arg1 and PPARγ compared to the MaR1-LD group (all P<0.05). MaR1 inhibits the classical activation of hippocampal microglia, promotes alternative activation, reduces sepsis-induced neuroinflammation, and improves cognitive decline.

Management factors associated with the survival and market weight of broiler chickens among small-scale farmers in the Dodoma City of Tanzania

Broiler chickens have the genetic potential for significant weight gain over a very short period of time. As a result, they account for over 92 % of the world's poultry meat production in different parts of the world. Yet, to fully realise their growth potential, effective management practices are crucial, encompassing aspects like nutritious feeds, disease control, optimal temperature, and adequate housing. The purpose of the study was to determine the management practices associated with the survival and market weight of broiler chickens in small-scale production. Small-scale poultry production plays a significant role in poverty reduction and household nutrition in developing countries. One hundred and forty small-scale broiler farmers were visited for interviews in the Dodoma City. Employing a structured questionnaire, data on management practices was gathered, while past production records determined market weight and survival rates. Most chickens weighed 1.8–2.3 kg at the end of the production cycle, with a mean live weight of 2.0 kg. Heat provision to chick housing in the early growth stages increased both survival and market weight. Conversely, chicken vaccination and the farmer's experiences were correlated with an increased survival rate. Furthermore, higher feed quantities offered to growers and finishers were linked to greater market weight. It was concluded that enhancing knowledge among small-scale farmers through training and extension services has the potential to increase broiler productivity.

Enhancing healthcare in the digital era: A secure e-health system for heart disease prediction and cloud security

In the modern world, due to changing lifestyles, more people are infected by deadly diseases, especially heart disorders. An early prognosis is the only possible way of increasing survival rate. One of the key elements of this context is the healthcare digitalization that is carried out through Internet of Things (IoTs) and cloud computing. However, main issue in cloud with IoT is false diagnosis, which leads to cause a major impact on patient’s life. Moreover, data communication through cloud servers can be compromised by attackers due to security issues. Therefore, to overcome these issues, this paper proposes a novel secure e-healthcare system with dual objectives- accurate disease prediction and improved cloud security. A novel diagnosis approach ‘Hybrid Binary Particle Firefly Optimized Extreme Learning Machine classifier (HybBPF-ELM)’ to predict HD is designed, that recognize the subject with HD abnormality from the normal ones. The prediction accuracy and time efficiency of training process are improved by the adoption of a Hybrid Binary Particle Firefly Optimizer (HBPFO) through fine-tuning weight and bias of Extreme Learning Machine (ELM) classifier. Additionally, a new intelligent encryption and decryption framework ‘IEDF’ is introduced for cloud security. It combines four encryption algorithms, including Advanced Encryption Standard (AES), Data Encryption Standard (DES), Rivest- Shamir-Adleman (RSA), and Modified Blow Fish (MBF) to enhance cryptographic strength and key security. Along with this, an Automatic Sequence Encryption (ASC) for data block encryption is employed to ensure strong security and network performance. The integration of HD prediction module and cloud security framework within e-healthcare system assists healthcare experts in securely storing and transferring data for advanced diagnosis. The results show that our proposed system achieves an overall prediction accuracy of 99.36 % and less processing time for encryption and decryption of 127.55 s and 452.01 s at 2.2 GB file size respectively.

Improved Preservation of Rat Small Intestine Transplantation Graft by Introduction of Mesenchymal Stem Cell-Secreted Fractions.

Segmental grafts from living donors have advantages over grafts from deceased donors when used for small intestine transplantation. However, storage time for small intestine grafts can be extremely short and optimal graft preservation conditions for short-term storage remain undetermined. Secreted factors from mesenchymal stem cells (MSCs) that allow direct activation of preserved small intestine grafts. Freshly excised Luc-Tg LEW rat tissues were incubated in preservation solutions containing MSC-conditioned medium (MSC-CM). Preserved Luc-Tg rat-derived grafts were then transplanted to wild-type recipients, after which survival, injury score, and tight junction protein expression were examined. Luminance for each graft was determined using in vivo imaging. The findings indicated that 30-100 and 3-10kDa fractions of MSC-CM have superior activating effects for small intestine preservation. Expression of the tight-junction proteins claudin-3, and zonula occludens-1 preserved for 24h in University of Wisconsin (UW) solution containing MSC-CM with 50-100kDa, as shown by immunostaining, also indicated effectiveness. Reflecting the improved graft preservation, MSC-CM preloading of grafts increased survival rate from 0% to 87%. This is the first report of successful transplantation of small intestine grafts preserved for more than 24h using a rodent model to evaluate graft preservation conditions that mimic clinical conditions.

Basic Life Support in Earthquake With Simulation Supported Training

Earthquakes are frequent natural disasters that can cause significant harm and loss of life. In recent years, there have been numerous major earthquakes worldwide. Nurses are crucial members of disaster response teams during earthquakes, providing vital interventions and basic life support to patients and the injured. This review study aims to help individuals learn the basic life support knowledge and skills necessary to increase survival rates and minimize injuries during natural disasters and emergencies through simulation training. Additionally, it provides an up-to-date approach to evaluating the effectiveness of disaster nurses. Nurses are crucial in promoting health, protecting public health, and providing basic life support to the community during all stages of a disaster, including mitigation, preparedness, response, and recovery. By doing so, they enhance the safety and resilience of the community. Simulation is an effective training method for teaching basic life support to disaster nurses. It provides opportunities for repeated practice in a safe and educational environment, facilitating different learning strategies.

DIPG-35. OVERCOMING THE BLOOD-BRAIN BARRIER CHALLENGE IN DIFFUSE MIDLINE GLIOMA

Abstract Diffuse midline gliomas (DMGs) are aggressive paediatric brainstem tumours with no known cure. The development of effective treatments is greatly impeded by the failure of most anti-tumour agents to penetrate the blood-brain barrier (BBB). Our research, along with that of others, has revealed that the BBB remains intact in DMG. We employed DMG orthotopic models to explore potential region-specific variations in response to the therapeutic agent temsirolimus as well as confocal microscopy and single-cell RNA sequencing (scRNAseq) to elucidate the impact of DMGs on brain endothelial morphology and pathways governing BBB integrity. We first assessed the effectiveness of the mTOR inhibitor temsirolimus when administered in cortex-injected DMG models compared to brainstem-injected DMG. We found significantly increased survival rates, elevated temsirolimus levels, and reduced tumour cell proliferation in the cortex versus the brainstem. Confocal imaging analysis indicated no structural differences between DMG and Matrigel-injected animals. However, scRNAseq unveiled distinct transcriptomic changes: brainstem-injected DMG exhibited downregulation of genes related to inflammatory and apoptotic pathways, whereas cortex-injected DMG showed downregulation of interferon pathways. To overcome the tightened barrier in the brainstem, we explored three MCL1 inhibitors and SNGR-TNFa (targeting CD13) as potential blood-brain barrier modulators. These inhibitors significantly reduced transendothelial electrical resistance, increased tracer dye leakage in an in vitro DMG BBB model, and decreased the protein expression of claudin-5. Moreover, in vivo, we found that administration of a single dose of either SNGR-TNFa or the MCL1 inhibitor S63845 improved penetration of Texas-Red (3KDa) in DMG-engrafted animals, indicating the effective opening of the BBB. In summary, our study revealed that DMG directly affects BBB pathways in endothelial cells, tightening the barrier and reducing treatment efficacy. MCL1 inhibitors and SNGR-TNFa show promise in modulating the BBB and have the potential to enhance therapeutic activity.