Higher Survival Research Articles

Polyvinyl Alcohol Hydrogel Hemiarthroplasty of First Metatarsophalangeal Joint Hallux Rigidus.

Background Hallux rigidus (HR) is the most common arthritic condition of the foot. Although first metatarsophalangeal joint (MTPJ) arthrodesis has been the historical gold-standard treatment, polyvinyl alcohol (PVA) hydrogel implants have gained popularity as a joint-sparing technique. However, recent studies have shown variable failure rates of PVA hydrogel implants. The purpose of this study was to report the five-year experience with PVA hydrogel implants performed by a single surgeon. Methodology Health records were queried from August 2016 to 2021 for patients who underwent primary PVA hydrogel implant hemiarthroplasty for symptomatic late-stage HR. Patient demographics and postoperative outcomes variables were evaluated. Kaplan-Meier analysis was used to evaluate implant survival. A total of 146 PVA hydrogel implant procedures were performed with a minimum six-month follow-up. Results The majority of patients were female (n = 103, 70.5%), with a mean age of 58.1 (±10.1) years, body mass index of 27.3 (±5.2) kg/m2, and American Society of Anesthesiologists score <3 (n = 131, 89.7%).The majority had stage II or III disease (n = 115, 78.8%). Patients experienced significant improvement in visual analog scale score (p < 0.0001) and hallux dorsiflexion (p = 0.0005). There were 22 (15.1%) complications, including implant subsidence (n = 15, 10.3%), deep infection (n = 6, 4.1%), and hypertrophic ossification (n = 1, 0.7%). Revision surgeries were required in 12.3% (n = 18) of patients at an average of 9.4 (±9.2) months postoperatively. This included nine (6.2%) revision PVA hydrogel implant procedures and nine (6.2%) first MTJP arthrodesis. The one- and two-year survival rates for MTPJ arthrodesis (n = 9) were 95.9% and 86.3%, respectively. Conclusions In the largest single-surgeon series reported, first MTPJ hemiarthroplasty with a PVA hydrogel implant significantly improved pain and hallux dorsiflexion at an average of 14.5 months postoperatively. There was a high two-year survivorship of 86.3% until failure which required first MTPJ arthrodesis. Future studies should be performed to refine the indications for PVA hydrogel implants and identify risk factors.

Exploration of the Correlation Between GRHL1 Expression and Tumor Microenvironment in Endometrial Cancer and Immunotherapy.

GRHL1 belongs to the family of Grainyhead-like (GRHL). Previous studies have shown that dysregulation of growth and survival pathways is associated with the GRHL family of gene cancers. Immunotherapy with checkpoint inhibitors has changed the treatment paradigm for many tumors, including endometrial cancer (EC). However, the effect of GRHL1 on immunotherapy in EC and its relationship with immune cell infiltration are poorly understood. Differential expression of GRHL1 between EC and normal EC tissues was analyzed by searching the TCGA database, and the results were verified utilizing immunohistochemistry analyses. Next, the relationship between GRHL1, CD8+ T cells and tumor microenvironment (TME) was also investigated, and the effect of GRHL1 expression on immunotherapy in EC was evaluated. According to the findings, EC tissues had elevated expression levels of GRHL1 relative to normal tissues. Patients with EC who expressed GRHL1 at high levels experienced worse overall survival (OS) and Progression-free survival (PFS) than those whose expression was lower. In addition, GRHL1 expression was negatively correlated with CD8+ T cells, and patients with high GRHL1 expression were less effective in receiving immunotherapy. The expression of GRHL1 was high in EC patients, and high expression of GRHL1 inhibits the proliferation of CD8+ T cells in the tumor microenvironment of EC and affect the efficacy of immunotherapy.

Selection among critically endangered landlocked salmon (Salmo salar m. sebago) families in survival and growth traits across early life stages and in different environments.

Endangered wild fish populations are commonly supported by hatchery propagation. However, hatchery-reared fish experience very different selective pressures compared to their wild counterparts, potentially causing genotype-by-environment interactions (G × E) in essential fitness traits. We experimentally studied early selection in a critically endangered landlocked Atlantic salmon population, first from fertilization to the swim-up stage in a common hatchery setting, and thereafter until the age of 5 months in two contrasting rearing environments. Swim-up progeny were moved either to standard indoor hatchery tanks involving conventional husbandry or to seminatural outdoor channels providing only natural food. After the first summer, sampled survivors were assigned to their families by genotyping. Early survival until the swim-up stage was mostly determined by maternal effects, but also involved significant variation due to sires and full-sib families (potential genetic effects). High on-growing survival in hatchery tanks (88.7%) maintained a more even distribution among families (relative share 1.5%-4.2%) than the seminatural environment (0.0%-5.4%). This heterogeneity was mostly maternal, whereas no independent paternal effect occurred. Heritability estimates were high for body size traits in both environments (0.62-0.69). Genetic correlations between the environments were significantly positive for body size traits (0.67-0.69), and high body condition in hatchery was also genetically linked to rapid growth in the seminatural environment (0.54). Additive and phenotypic growth variation increased in the seminatural environment, but scaling effects probably played a less significant role for G × E, compared to re-ranking of genotypes. Our results suggest that not only maternal effects, but also genetic effects, direct selection according to the environmental conditions experienced. Consistently high genetic variation in growth implies that, despite its low overall genetic diversity and long history in captive rearing (>50 years), this landlocked Atlantic salmon population still possesses adaptive potential for response to change from hatchery rearing back to more natural conditions.

Survival Analysis Based Qos Recommendation for Bus Transportation using Deep Learning

Public transportation play an important role in metropolitan cities.Bus services are an important part of public transportation systems, which are frequently chosen because they are convenient, economical, environmentally beneficial, and less taxing on the infrastructure. The temporal patterns of bus transportation incidents are examined in this study using survival analysis, with a focus on the amount of time until certain events like delays, malfunctions, or safe arrivals at destinations. High-dimensional data is being generated at an increasing rate due to technological advancements. As a result, it is quite difficult to analyze such a dataset adequately. Algorithms for machine learning (ML) have become popular tools for modeling complex and nonlinear interactions in a variety of real-world applications, including as the analysis of high-dimensional survival data. Multilayer Deep Neural Network (DNN) models have achieved impressive results recently. Thus, using Keras and TensorFlow, a Cox-based DNN prediction survival model (DNNSurv model) was created. Its findings, however, were limited to survival datasets with large sample sizes or high dimensionality. Using high dimensional survival data, the proposed work will evaluate the DNNSurv model's prediction ability and compare it to a well-known machine learning survival prediction model (random survival forest). The Proposed Work also offers the best settings for a number of hyperparameters, including tuning parameter selection, for this reason. The suggested approach showed through data analysis that, when compared to the ML model, the DNNSurv model performed better overall in terms of the two primary survival prediction evaluation measures (i.e., the concordance index and the time-dependent AUC).

Different Scenarios for the Origin and the Subsequent Succession of a Hypothetical Microbial Community in the Cloud Layer of Venus.

The possible existence of a microbial community in the venusian clouds is one of the most intriguing hypotheses in modern astrobiology. Such a community must be characterized by a high survivability potential under severe environmental conditions, the most extreme of which are very low pH levels and water activity. Considering different scenarios for the origin of life and geological history of our planet, a few of these scenarios are discussed in the context of the origin of hypothetical microbial life within the venusian cloud layer. The existence of liquid water on the surface of ancient Venus is one of the key outstanding questions influencing this possibility. We link the inherent attributes of microbial life as we know it that favor the persistence of life in such an environment and review the possible scenarios of life's origin and its evolution under a strong greenhouse effect and loss of water on Venus. We also propose a roadmap and describe a novel methodological approach for astrobiological research in the framework of future missions to Venus with the intent to reveal whether life exists today on the planet.

Fire has contrasting effects on the survival, growth, and reproduction of Cerrado grasses with differing regenerative strategies

AbstractBackgroundCerrado grasses are closely linked to fire, but the mechanisms underlying their responses are poorly understood. Fire affects populations by altering vital rates, and different regenerative strategies likely influence responses as resprouting ability trades off with seeding investment. Specialist grasses mostly occupy old‐growth habitats and rely almost entirely on vegetative regeneration, suggesting potentially higher fire tolerance than habitat generalists that can colonize anthropized and degraded habitats due to high seeding investment. Thus, we explored the effect of fire on one specialist (Trachypogon spicatus) and two generalist (Aristida riparia and Schizachyrium microstachyum) tussock grasses.LocationFrequently burned grassland in Central Brazil.MethodsWe monitored the vital rates of 150 individuals/species in burned (prescribed late‐dry‐season fire) and unburned plots. Survival, resprouting, and reproduction were assessed monthly for six months post‐fire and then again 16 months after fire. Tussocks were measured for size (area of the base) and vegetative height for changes in structure. We collected seed mass, seed fill, and germination rates from the literature.ResultsFire negatively affected the generalist grasses, increasing mortality (+12%), decreasing size (50%), and inhibiting flowering and inflorescence production. The specialist benefited from burns, showing high survival (97%), recovery of pre‐fire structure, and stimulated reproduction. Generalist species had a high investment in seeds (seed fill &gt; 60%; germination &gt; 50%), while the specialist produced empty seeds (88%) with low germination (3%). Size was not related to the probability of survival but significantly increased the reproductive output.ConclusionsResults suggest that the specialist Trachypogon spicatus could persist under very frequent fires (e.g., annual), given its robust fire tolerance and post‐fire recovery. Where this species is a restoration priority, it would likely benefit from techniques that promote vegetative regeneration rather than direct seeding. Contrarily, generalist grasses are less resilient to fires and require longer fire intervals to allow population persistence.

Reproductive qualities of sows of different intrabreed differentiation according to some selection indexes and the economic efficiency of their use

The paper presents the study results of the absolute indicators of the reproductive qualities of sows of different intrabreed differentiation according to the breeding index of reproductive qualities of the sow (BIRQS) and the index of M. D. Berezovskyi, as well as the calculation of the economic efficiency of their use in the conditions of a controlled population. The research was carried out in the breeding breeder for breeding pigs of the large white breed of the experimental farm and the laboratory of animal husbandry and fodder production of the Institute of Agriculture of the North-East of the NAAS, as well as the laboratory of animal husbandry of the State Institution of Grain Crops of the NAAS. Evaluation of sows for reproductive qualities was carried out considering the following signs: multifertility, high fertility, nest weight at the time of weaning at 28 days, preservation. Comprehensive evaluation of sows for reproductive qualities was carried out according to the selection index of reproductive qualities of the sow (BIRQS) (Tsereniuk et al., 2010) and the index of M. D. Berezovskyi (Vashchenko, 2019). Biometric processing of research results was carried out according to generally accepted methods (Kovalenko et al., 2010). Taking into account the intrabreed differentiation according to the selection index of the reproductive qualities of the sow (BIRQS) and the index of M. D. Berezovskyi, a significant difference was established between the sows of the I and III experimental groups in terms of multifertility (2.8-2.4 heads), as well as the weight of the nest at the time of weaning at the age of 28 (16.9-16.0 kg) and 60 days (45.2-43.0 kg). The maximum indicators of high fertility and survival of piglets until weaning at the age of 28 days were found in sows of the III group of intrabreed differentiation according to the breeding index of reproductive qualities of the sow (BIRQS) and the index of M. D. Berezovskyi. The number of reliable pairwise correlation coefficients between the absolute indicators of reproductive qualities of sows, the index of M. D. Berezovskyi and the selection index of reproductive qualities of the sow (BIRQS) is 92.85%. The criteria for selecting highly productive sows are the following indicators: according to the index of M. D. Berezovskyi – 40.63-44.37 points, the selection index of reproductive qualities of the sow (BIRQS) – 98.13-108.98 points. The maximum increase in additional production was obtained from sows of the 1st experimental group of intrabreed differentiation according to the index of M. D. Berezovskyi (+9.49%) and the selection index of reproductive qualities of the sow (BIRQS) (+9.00%), and its value was +1002.92 and +951.14 UAH/head/farrow, respectively

Characterization of Probiotic Properties and Whole-Genome Analysis of Lactobacillus johnsonii N5 and N7 Isolated from Swine.

In our previous microbiome profiling analysis, Lactobacillus (L.) johnsonii was suggested to contribute to resistance against chronic heat stress-induced diarrhea in weaned piglets. Forty-nine L. johnsonii strains were isolated from these heat stress-resistant piglets, and their probiotic properties were assessed. Strains N5 and N7 exhibited a high survival rate in acidic and bile environments, along with an antagonistic effect against Salmonella. To identify genes potentially involved in these observed probiotic properties, the complete genome sequences of N5 and N7 were determined using a combination of Illumina and nanopore sequencing. The genomes of strains N5 and N7 were found to be highly conserved, with two N5-specific and four N7-specific genes identified. Multiple genes involved in gastrointestinal environment adaptation and probiotic properties, including acidic and bile stress tolerance, anti-inflammation, CAZymes, and utilization and biosynthesis of carbohydrate compounds, were identified in both genomes. Comparative genome analysis of the two genomes and 17 available complete L. johnsonii genomes revealed 101 genes specifically harbored by strains N5 and N7, several of which were implicated in potential probiotic properties. Overall, this study provides novel insights into the genetic basis of niche adaptation and probiotic properties, as well as the genome diversity of L. johnsonii.

A prospective and consecutive study assessing short-term clinical and radiographic outcomes of Chinese domestically manufactured 3D printing trabecular titanium acetabular cup for primary total hip arthroplasty: evaluation of 236 cases.

We prospectively evaluate the short-term clinical and radiographic outcomes of the only Chinese domestically produced trabecular titanium acetabular cup(3D ACT™ cup) in primary total hip arthroplasty (THA), aiming to provide evidence-based support for its clinical application. A total of 236 patients, who underwent primary THA using 3D ACT™ cup in the Department of Joint Surgery at our hospital between January 2017 and June 2019, were included in this study. General patient data, imaging information, functional scores, and complications were collected to evaluate the early clinical efficacy. All patients were followed up for 33-52 months, with an average of (42.2 ± 9.2) months. At the last follow-up, the preoperative HHS score increased significantly from 43.7 ± 6.8 to 85.6 ± 9.3 points (P < 0.01). Similarly, the preoperative WOMAC scores showed significant improvement from 59.2 ± 5.8 to 13.1 ± 3.5 points (P < 0.01). 92.3% of the patients expressed satisfaction or high satisfaction with the clinical outcome. Furthermore, 87.7% of the acetabular cups were positioned within the Lewinnek safe zone, achieving successful reconstruction of the acetabular rotation center. The cup survival rate at the last follow-up was 100%. The utilization of the only Chinese domestically manufactured 3D printing trabecular titanium acetabular cup in primary THA demonstrated favorable short-term clinical and radiographic outcomes. The acetabular cup exhibits excellent initial stability, high survival rate, and favorable osseointegration, leading to a significant enhancement in pain relief and functional improvement. In the future, larger sample sizes and multicenter prospective randomized controlled trials will be required to validate the long-term safety and effectiveness of this 3D ACT™ cup.

Tree species with potential for reforestation in coastal zones of the humid tropics

Aim of study: The native species of warm humid climates Ceiba pentandra, Tabebuia rosea, Gliricidia sepium, Enterolobium cyclocarpum and Brosimum alicastrum are often included in Mexican reforestation programs. We evaluated the growth response in sandy soils of these species that could serve as pioneers in the restoration of coastal areas. Area of study: Alluvial plain in Frontera, Tabasco, Mexico. Material and methods: A total of 1080 plants were planted in 2014 and evaluated for 23 months in 30 plots under a randomized block design with six replications. The sample plots each occupied 36 m2 (each with 16 plants). Survival percentage, stem height (SH), basal diameter (BD) and basal area (BA) were quantified. Survival and growth variables were analyzed using logistic regression and ANOVA for repeated measures, respectively. Main results: At the end of the experiment (2016), high survival was demonstrated in G. sepium (88 %) and in C. pentandra (86 %), while B. alicastrum presented total mortality at six months. The highest values of SH and BD were presented in C. pentandra (2.9 m and 7.8 cm, respectively) and in G. sepium (2.6 m and 4.2 cm, respectively). Gliricidia sepium differed significantly from C. pentandra in terms of BA (5.9 vs. 23 m2 ha-1, respectively). Research highlights: The native species C. pentandra and G. sepium presented high survival and growth in the sandy soils; G. sepium showed strong adaptation to the environment and C. pentandra offered suitable coverage, characteristics that are necessary for the success of reforestation and restoration programs.

Enhancing Leaf Nutrient Levels in Polyembryonic Mango (Mangifera indica L.) Seedlings: The Impact of Saline Water Irrigation and 28-Homobrassinolide Spray

The leaf nutrients play a key role in the growth of a plant. Therefore, a study was undertaken to evaluate the effect of saline water and spray of 28-homobrassinolide on leaf nutrient status of polyembryonic mango (Mangifera indica L.) seedling during the years 2021-22 and 2022-23 at Agriculture Experimental Station, Navsari Agricultural University, Paria, (Gujarat). The experiment was laid out in Completely Randomized Design with factorial concept comprising of four salinity levels [S1: Best available water (control), S2: 2 dS m-1, S3: 4 dS m-1, S4: 6 dS m-1] and three spray concentration of 28-homobrassinolide [H1: No spray, (control), H2 : 0.5 ppm and H3 : 1 ppm]. Saline water application and 28-homobrassinolide spray was started at 80 days after sowing up to 240 days. The treatment containing application of water having lowest salinity (best available water) resulted in significantly higher leaf nutrient contents except Na up to 9 months after sowing during both years and in pooled analysis. Application of saline water having EC 6 dS m-1 adversely affected the growth of polyembryonic mango seedlings, reduced nutrient contents after 6 months of sowing. After 6 month of sowing, highest nutrient contents except Na was noted in mango seedlings treated with spray of 1 ppm 28-homobrassinolide during both years and in pooled analysis. The interactions of salinity levels and 28-homobrassinolide spray significantly affect leaf nutrient content of mango seedlings. Leaf nutrient contents except Na up to 9 months after sowing during both the years and in pooled analysis were recorded in treatment combination of best available water along with 1 ppm spray of 28-homobrassinolide. Maximum content of Na was observed in plants irrigated with 6 dS m-1 salinity level without spray of 28-homobrassinolide. Hence, it can be concluded that polyembryonic mango seedlings can be grown with saline irrigation having salinity up to 4 dS m-1 along with 1 ppm 28-homobrassinolide spray for better growth, biomass, nutrient contents and higher survival up to 9 months after sowing.

Comparative analysis of the growth performance, vitality, body chemical composition and economic efficiency of the main cultivated strains of Pacific white shrimp (Litopenaeus vannamei) in coastal areas of China

The Pacific white shrimp (Litopenaeus vannamei) is known for its fast growth, strong resistance to adversity, and high adaptability to various environments, which results in significant economic benefits. This study aimed to explore a simple and effective method for farmers to choose high-quality L. vannamei strains with fast growth, high survival rate, low transportation mortality rate, and high economic benefits. In this study, the three main cultivated strains (that is, “Haixingnong”, “Hairen”, and “Huanqiu” strains) of shrimp in coastal areas of China were used to compare the growth performance, survival, ability of dry stress tolerance and jumping, nutritional composition, and aquaculture economic benefits under greenhouse cultivation conditions by measuring and calculating the basic parameters of different strains, recording the survival rates of dry stress at different temperatures, statistics of bounce heights, official methods of official analytical chemicals international, and break-even analysis. The results showed that, after 122 days cultivation, there was no difference of growth performance and survival rate among the three strains (P > 0.05). The dry stress tolerance of “Hairen” strain shrimp was more affected by temperature, while “Haixingnong” strain was the least affected by temperature. The jumping ability and muscle burst strength of “Huanqiu” and “Hairen” strains were significantly stronger than “Haixingnong” strain (P < 0.05). Furthermore, for the amino acid score (AAS) and chemical score (CS) in the three strains, there was no significant differences between Phe and Lys (P > 0.05), but the Thr, Val, Met, Ile, and Leu was significantly lower in “Huanqiu” strain than “Haixingnong” and “Hairen” strains (P < 0.05). According to the sensitivity analysis of the three strains, the sensitivity coefficients were ranked as follows: “Hairen” strain > “Huanqiu” strain > “Haixingnong” strain. The smaller the sensitivity coefficient, the stronger the ability to withstand market price fluctuation risk, therefore “Haixingnong” strain had the strongest ability to resist market price risk. It is worth noting that the feed coefficient of “Haixingnong” strain was significantly lower than that of the other two strains, and the net profit of “Haixingnong” strain was the highest among the three L. vannamei strains, indicating that farmers would have lower investment costs if they raised the “Haixingnong” strain. In summary, although “Huanqiu” and “Hairen” strains exhibited advantages in dry stress tolerance and jumping ability, a comprehensive assessment of growth performance and economic benefits in actual aquaculture indicated that the “Haixingnong” strain can bring more economic benefits to farmers.

Impacts of greenhouse fertilization and planting season on survival and reproductive potential of Silene regia transplants

Restoration of rare plants is essential to maintain species diversity in natural areas. The methods used to grow and plant these rare plants for restoration impact seedling health and potentially the success of restoration attempts. We evaluated how different fertilizers and planting seasons impacted survival and reproductive potential for transplants of Silene regia. Plants were grown from seeds in greenhouses with four fertilizer treatments: slow‐release, liquid biweekly (every other week), liquid weekly, and control (no fertilizer). Transplanting was conducted in spring and fall for 2 years (2010 and 2011) at three sites. Number of leaves on transplants were counted before planting. Plants were counted over the growing seasons for 8 years (2010–2017) to determine survival and stem elongation (an indication of reproductive potential). Transplants produced the most leaves with slow‐release, followed by both liquid fertilizers and the fewest leaves with no fertilizer. The fertilizer type had a limited effect, but plants grown with fertilizer had increased survival and stem elongation relative to no fertilizer when a fertilizer effect was found. Planting season had a more consistent effect, with spring having higher survival and stem elongation. Sites differed for all measured parameters. Year‐to‐year survival was initially high, then dropped after 3–5 years, and less than 20% of plants remained by 2017. These findings demonstrate the value of pre‐planting fertilizer to provide vigorous transplants and planting season for reintroductions. Finally, multiple sites and long‐term monitoring are important to ensure success for reintroductions of rare species such as S. regia.

Voltinism and life‐history traits of the invasive fall armyworm Spodoptera frugiperda (Lepidoptera: Noctuidae) feeding on corn

AbstractVoltinism and life‐history traits of the invasive fall armyworm (FAW) Spodoptera frugiperda were investigated under semi‐natural conditions for a period of 2 years. The FAW invaded the corn field in the suburbs of Nanchang (28°46′ N, 115°50′ E) in early summer and produced six complete generations. FAW had the characteristics of short developmental time, high survival rates and strong fecundity. The development time of female pupae was significantly faster than that of male pupae, resulting in the emergence of female pupae earlier than male pupae. Except for the sixth generation in 2021, there was no significant difference between female and male sex ratio, which was close to 1:1. FAW showed male‐bias sexual size dimorphism with male pupae being significantly larger than female pupae. Unlike pupal weight, in most generations, male adult weighed significantly less than females, because the weight loss of male pupae during metamorphosis was significantly greater than that of female pupae. The temporal variation of pupal weight did not conform to the temperature–size rule. Compared with 22.8°C, the 29.2°C high temperature not only significantly reduced the development time of larvae but also significantly increased pupal weight. The adult fecundity feeding on fresh corn leaves was higher than that feeding on live corn plants in most generations. In most generations, pupal weight was positively correlated with larval development time and adult weight was positively correlated with fecundity. In conclusion, climate differences between generations and years have significant effects on developmental time, body weight, sexual size dimorphism and fecundity of the FAW. These results add to the understanding of the evolution of life‐history traits in the FAW and may have important implications for predicting population dynamics of the FAW and optimising control strategies.

Effect of three probiotic Bacillus strains supplemented feeds on growth, carcass composition and blood parameters of Clarias magur (Hamilton)

ABSTRACT Lysinibacillus sphaericus PKA17, Bacillus cereus PKA18 and Bacillus thuringiensis PKA19, isolated from the intestine of adult indigenous magur (Clarias magur), were evaluated as putative probiotics for the cultivation of C. magur fingerlings. A total of 180 magur fingerlings (average weight 4.01 ± 0.01 g) were randomly distributed into four dietary groups in triplicate. The fingerlings were cultivated for 120 days into continuous-flow experimental rectangular cemented tanks (195 × 105 × 90 cm3; 1600 l; 5 cm bottom mud). Probiotics were mixed in feed (PT1: 2 × 106 L. sphaericus PKA17 cells; PT2: 2 × 106 B. cereus PKA18 cells; PT3: 2 × 106 B. thuringiensis PKA19 cfu/kg of basal feed where, PT = Probiotic treated) and fed to different dietary groups of fish. However, the control feed comprises of basal ingredients, and was not supplemented with any bacterial isolate. Fish carcass composition revealed significantly (p < 0.05) higher amounts of carbohydrate (2.8 ± 0.06 g kg−1), iron (2.21 ± 0.01 mg 100 g−1), fat-soluble vitamins and amino acid in fish fed PT1 than other groups. Fish fed PT1 feed also displayed a considerably higher protein efficiency ratio (2.05 ± 0.01) and lower feed conversion ratio (1.23 ± 0.01). Higher carcass protein content (164.9 ± 0.23 g kg−1) was observed in fish fed PT3 feed followed by PT1 and PT2. Fish fed probiotic-supplemented feed (PT1, PT2, and PT3) showed higher amounts of high-density lipoprotein and calcium than the control-fed fish. High survivability was observed in fish fed probiotic-feed compared to the control group. The results suggest that feed (PT1, PT2, PT3) incorporated with these probiotics might enhance the growth of C. magur in captivity, which may promote the cultivation of this endangered species.

Abstract 144: Sex bias in neuroblastoma: Worse outcomes for female patients are associated with dysregulation of DLK1 and H19

Abstract Neuroblastoma (NB) is a devastating neural crest-derived tumor primarily affects children under five. Forty percent of NB patients are classified as high-risk (HR), and less than half of them survive. HR disease is split into two equally sized groups: one exhibiting genetic amplification of the MYCN proto-oncogene (MA), and another where MYCN is non-amplified (MNon). Overall survival (OS) studies are often either poorly annotated or focused on outcomes across the entire patient group, which may mask differential outcomes or biases among NB subgroups. Here we report our assessment of OS among several genetic, histopathological, and sex-based subgroups in three different well annotated NB patient datasets. Our analysis reveals a previously unseen sex-bias in HR MNon patients, where female patients have significantly worse OS than males. This disparity carries into stage 4s NB, defined by high survival in infants despite the presence of broadly disseminated disease. In stage 4s patients across two studies, we observe no deaths among males (n=66) and 6 among females (n=48), again marking significantly worse OS in females. Expression analysis comparing male and female HR MNon patients identifies DLK1 and H19, two imprinted genes implicated in multiple malignancies, as frequently overexpressed in females. A similar pattern is seen in RNA seq analysis of human MA (n=4) and MNon (n=4) cell lines. In addition, both DLK1 and H19 are associated with worse prognosis in female but not male patients. We also report that depletion of either gene results in reduced growth in vitro. Moreover, the NB-related ATRX tumor suppressor has been shown to inhibit H19 via insertion of histone variant H3.3. We observe an inverse correlation between H3.3B and H19 expression in female HR MNon patients. Further, H19 levels increase upon ATRX depletion in human NB cells, suggesting that ATRX indeed regulates H19 in NB. These findings provide the first evidence of female-biased outcomes in NB and suggest functional involvement of DLK1, H19 and ATRX. Citation Format: Mariya Raleigh, Vishwa Patel, Lorraine R. Benhamou, Xin Shen, Dennis A. Sheeter, Erika C. Espinosa, Niharika Reddy Badi, Chase Calvert, Garrett Bourne, John T. Powers. Sex bias in neuroblastoma: Worse outcomes for female patients are associated with dysregulation of DLK1 and H19 [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 144.

Abstract 7394: Delineating spatial expression signatures of lung adenocarcinoma subtypes from spatial single-cell transcriptomics using graph neural networks

Abstract Lung Adenocarcinoma (LUAD) subtypes including complex acinar (CA), micropapillary, and solid regions are characterized by distinct morphological and biological features that bear significant implications for prognosis and treatment strategies. While histology-based subtype prediction has provided a structural understanding, it overlooks crucial biological insights related to molecular mechanisms and the influences of tumor microenvironments (TMEs). Recent advances in spatially resolved single-cell profiling enable precise measurements of gene expression at the cellular and sub-cellular levels within intact tissues. We hypothesize that spatial gene expression (SGE) patterns can effectively identify LUAD subtypes and characterize the influence of TMEs. Thus, to address the limitations of histology-based subtyping of LUAD, we developed an AI-driven approach that leverages SMI samples to predict LUAD subtypes and elucidate their underlying molecular landscape and associated TMEs. For this study, we leverage the NanoString CosMx Spatial Molecular Imaging (SMI) NSCLC FFPE datasets comprising of 8 LUAD tissue samples, annotated by pathologists at UPMC for subtype identification. The dataset consists of approximately 98k cells per sample with 18 cell types and 960 genes per cell. We encoded the spatial organization of cells as a graph with nodes representing cells with expression features and edges based on k-nearest neighbors of 30 cells. We considered the prediction of micropapillary, CA, and solid for each tumor cell and developed a Graph Convolutional Network (GCN) with semi-supervised training to account for the unlabeled nodes. A subgraph splitting strategy with cross-validation was developed to train on localized spatial regions and ensure balanced label proportions in each subgraph. Our GCN achieved 92.63% test accuracy, surpassing non-spatial deep learning models (77.45%). Notably, explanation analysis using the GNNExplainer algorithm of our trained model identified high-attribution cells in CA and solid TME, revealing unique differentially expressed genes (DEGs) - JUNB in CA, and VIM, GPX1, PSAP, IFI27 in solid tumors, compared to low-attribution cells within the same subtype. Further analysis revealed an enrichment of EMT and interferon alpha/gamma, suggesting a more inflamed phenotype than low-attribution cells. Differential expression analysis of high-attribution CA vs solid cells identified significant upregulation of NDRG1 in CA and COL1A1 in solid. Functional enrichment analysis of these DEGs revealed PI3k-Akt in CA and MAPK signaling pathway in solid, suggesting an aggressive solid TME and CA with high survival and metastasis. We further identified a distinct neutrophil-enriched TME associated with CA and revealed cell-cell communication through MIF interactions with the CD74/CXCR4 and CD44/CD74 axes. Citation Format: Arun Das, Md Musaddaqul Hasib, Zhentao Liu, Wen Meng, Yu-Chiao Chiu, Gabriel Sica, Shou-Jiang Gao. Delineating spatial expression signatures of lung adenocarcinoma subtypes from spatial single-cell transcriptomics using graph neural networks [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 7394.

Abstract 896: Predicting metastatic transcriptomes of patient tumors with deep learning

Abstract Metastases are the primary cause of cancer-related death, and improving the means of predicting and targeting their development is one of the major goals in cancer research. While surgical resection and neo-adjuvant therapy can cure well-confined primary tumors, our ability to effectively treat cancer is largely dependent on our capacity to interdict the process of metastasis. The recent accumulation of ‘omics data from metastatic tumors provides an unprecedented opportunity to develop machine learning models to predict the molecular changes during metastasis and explore the patterns of metastasis formation. With this in mind, we developed MetMapper, a deep learning model trained on primary and metastatic tumors from &amp;gt; 13 000 patients integrating data from 11 published data resources. MetMapper can predict the transcriptomic changes of a primary tumor when it metastasizes to different distant organs. The results were extensively validated using transcriptomics data from matched primary and metastatic tumor biopsies extracted from the same patients. Furthermore, MetMapper’s predictions revealed that the non-random patterns of cancer metastases can be partly explained by the degree of transcriptome reprogramming needed during metastasis: primary tumors tend to metastasize to organs that require minimal changes to their transcriptomes. Using MetMapper, we derived a metastatic potential score for patient tumors and demonstrate that this score can be used to stratify patients into high and low survival groups across different indications. The predicted metastatic potential of patient tumors significantly correlates with experimentally characterized metastatic potential of cancer cell lines. Additionally, by performing in-silico perturbations of genes and oncogenic pathways that can alter the metastatic potential of patient tumors, we identified genomic features that are highly associated with metastases to specific organs, some of which were reported by existing pan-cancer clinical sequencing studies. Our results demonstrate the utility of MetMapper as a novel AI-powered methodology for investigating mechanisms and patterns of metastatic dissemination, as well as forecasting metastatic outcomes of patient tumors. Citation Format: Gang Li, Evan Béal, Dean Sumner, Giorgio G. Galli, Viviana Cremasco, Joshua M. Korn, Frank Dondelinger, David Ruddy, Audrey Kauffmann, Slavica Dimitrieva. Predicting metastatic transcriptomes of patient tumors with deep learning [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 896.

Abstract 2387: Drivers of precision in oncology trials: A landscape analysis of biomarkers and treatments

Abstract Background: Molecular profiling is powerful to match patients’ tumor profile with targeted therapies in oncology. While our understanding of treatments and biomarkers that enhance overall response rates is growing, the level of consistency at which treatment response is assured in biomarker-enriched (BE) cohorts (e.g. immune-checkpoint inhibitors in PD-L1-positive tumors) remains poorly understood. In essence, an optimal biomarker would not only result in high mean survival but also precise, closely clustered response of all patients around this mean. Objectives: The primary objective of this study is to develop a method to measure the variability of survival outcomes from published Kaplan-Meier (KM) curves in trials. The secondary objective is to assess whether novel treatments, when given in the presence of predictive biomarkers, improve not only mean survival, but also its precision. This is clinically relevant as higher precision guarantees patients a treatment outcome closer to the mean, thereby providing safeguards against non-response. Methods: We conducted a criteria-based search in PubMed and EMBASE to identify all phase-II and -III drug trials on breast cancer and non-small cell lung cancer (NSCLC) published between 2018-2022. We developed an algorithm to derive pseudo-individual patient data (p-IPD) from KM curves. We measured variability of survival outcomes in treatment and control groups using ratios of coefficients of variation (CVRs) derived from log-normal models and restricted mean survival time. This novel computational approach enables comparing the consistency of treatment responses in BE subgroups versus total, i.e. intention-to-treat (ITT), populations in each trial. Results: From screening 780 publication records (NSCLC: n = 405; breast cancer: n = 375), we identified 67 biomarker-stratified drug trials (NSCLC: n = 41; breast cancer: n = 26). We successfully constructed p-IPD using KM curves from ITT and BE cohorts for the first 18 trials (NSCLC: n = 10; breast cancer: n = 8) from a total of 11,373 patients (NSCLC: n = 7,547; breast cancer: n = 3,826). The preliminary meta-analysis for overall survival on these first 18 trials shows that BE treatment groups respond more precisely, with a variability reduction from 0.93 [95%-CI: 0.91, 0.96] in the ITT group to 0.86 [0.83, 0.91] in the BE subgroup. This variability reduction varies across treatment, biomarker, and tumor types. Finally, we observe different variability estimates in trials (n = 6) that are stratified by subgroups of different PD-L1 expression. Conclusion: This is the first study that presents a viable approach to analyze the variability of biomarker-treatment pairs in oncology at large scale. We find a reduction of treatment variability in breast and lung cancer trials in BE populations. Our work offers an orthogonal approach to measure biomarker utility with the potential to inform biomarker discovery and trial design. Citation Format: Maximilian Schuessler, Elizaveta Skarga, Pascal Geldsetzer, Ying Lu, Maike Hohberg. Drivers of precision in oncology trials: A landscape analysis of biomarkers and treatments [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 2387.

Abstract 5140: ITGB6 as a predictive biomarker for overall prognosis and PD-(L)1 immune checkpoint blockade response in various cancer types

Abstract Our previous work studying the effects of integrin αvβ6 knockdown in cancer cells demonstrated αvβ6 as a method of T cell suppression in a co-culture model. ITGB6, the gene encoding the β6 subunit of αvβ6, is a potent prognostic marker across multiple cancer types. As a major activator of latent TGFβ, αvβ6, and consequently, ITGB6, has considerable therapeutic implications due to the immunosuppressive effect that activated TGFβ has on the tumor microenvironment. A Human Protein Atlas search of ITGB6 expression surveyed the upregulation of ITGB6 across cancer types. Cancer ITGB6 expression was then compared to expression in paired adjacent normal tissue using the TNMplot tool (Bartha, 2021) on a concatenated set of GEO, GTex, TCGA, and TARGET RNA-seq databases. Kaplan-Meier curves were generated using TCGA mRNA data through the cBio portal, splitting the cohorts according to an ITGB6 mRNA expression threshold of one standard deviation above the mean (z-score ± 1.0). ITGB6 expression and immune checkpoint blockade (ICB) response were evaluated with the Kaplan-Meier Plotter tool (Kovacs, 2023). ITGB6 expression levels between ICB responders and non-responders were quantified using the ROC Plotter tool (Fekete, 2023), and the figures were generated using Matplotlib in Python. Lung, bladder, head and neck, pancreatic, and cervical cancer all demonstrated high expression of ITGB6. Head and neck squamous cell carcinoma (median fold change 2.70, p&amp;lt;0.0001), bladder urothelial carcinoma (FC 2.41, p&amp;lt;0.001), cholangiocarcinoma (FC 5.33, p&amp;lt;0.01), and esophageal carcinoma (FC 2.72, p&amp;lt;0.03) showed strong upregulation of ITGB6 compared to normal tissue. Interestingly, lung adenocarcinoma (FC 0.77, p&amp;lt;0.04) and lung squamous cell carcinoma (FC 0.55, p&amp;lt;0.0001) showed downregulation of ITGB6 compared to normal tissue. Survival data revealed that ITGB6 was a potent marker of a poor prognosis in pancreatic adenocarcinoma (high ITGB6 median survival 16.79 mos, vs. low ITGB6 21.88 mos, p&amp;lt;0.004) and head and neck squamous cell carcinoma (high ITGB6 30.06 mos vs. low ITGB6 57.42 mos, p&amp;lt;0.03). However, no significant prognostic difference was observed in non-small cell lung cancers. Finally, high pan-cancer expression of ITGB6 led to poorer response to αPD-1 (high ITGB6 Hazard Ratio 1.37, p&amp;lt;0.05) and αPD-L1 (high ITGB6 HR 1.50, p&amp;lt;0.001). In vitro and in vivo experiments to validate the benefit of ITGB6 as a biomarker and as a therapeutic target are underway. Citation Format: William J. MacDonald, Praveen R. Srinivasan, Maximilian Pinho-Schwermann, Vida Tajiknia, Connor Purcell, Lindsey Carlsen, Wafik S. El-Deiry. ITGB6 as a predictive biomarker for overall prognosis and PD-(L)1 immune checkpoint blockade response in various cancer types [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 5140.