Biological Characteristics Research Articles

Thyrotropin (TSH) and thyroid autoimmunity are predictive factors for the incidental discovery of papillary thyroid microcarcinoma during thyroidectomy.

To identify clinical, biological and pathological risk factors for the incidental discovery of papillary thyroid microcarcinomas (PTMCs) in patients undergoing thyroidectomy for presumed benign conditions. Cross sectional, single center study, involving all consecutive patients (N = 3015) who were submitted to thyroid surgery between 2001-2019. All medical files were retrospectively reviewed. A total of 1961 patients in the benign group and 145 patients in PTMC group were analyzed. No significant differences in age, sex, body mass index, smoking status, thyroid volume or weight and preoperative thyroxine treatment between benign and PTMC groups were observed. Circulating anti- thyroid antibodies, histological thyroiditis and serum thyrotropin (TSH) were significantly associated with PTMC in univariable analysis. Independent risk factors for incidental PTMC by multivariable analysis where possible (OR: 1.51, 95% CI: 0.99-2.28) and certain (OR: 1.74, 95% CI: 1.09-2.78) thyroid autoimmunity (p = 0.002) and higher serum TSH (OR: 1.25, 95% CI: 1.08-1.45, p = 0.03), whereas thyroid lobectomy was associated with a lower risk of PTMC (OR: 0.40, 95% CI: 0.24-0.67, p < 0.001). The most frequent genetic alteration was BRAFV600E mutation, found in 56.3% of PTMC submitted to DNA sequencing. No association between clinical, biological or histological characteristics of PTMC and BRAFV600E mutation was observed. Thyroid autoimmunity and higher preoperative serum TSH level were independent predictors of PTMC incidentally discovered during thyroid surgery. Larger prospective studies are needed to better identify possible risk factors for papillary thyroid carcinoma initiation and progression.

Growth hormone increase by luteinizing hormone-releasing hormone reflects gonadotroph-related characteristics in acromegaly.

We previously showed the clinical characteristics of acromegaly with a paradoxical growth hormone (GH) response to oral glucose or thyrotropin-releasing hormone. However, the clinical characteristics of acromegaly with an increased GH response to luteinizing hormone-releasing hormone (LHRH responders) remain unclear. The aim of the present study was to evaluate the clinical characteristics, especially gonadotroph-related characteristics of LHRH responders in acromegaly. The clinical characteristics of 33 LHRH responders and 81 LHRH nonresponders were compared. No differences in age, sex or basal serum levels of GH, insulin-like growth factor-1 (IGF-1), and gonadotropin were observed between the two groups. Steroidogenic factor 1 (SF-1), gonadotropin-releasing hormone receptor (GnRHR), and LH expression was more frequently observed in LHRH responders (P < 0.05). In addition, a greater increased rate of GH after LHRH loading, and the proportion of GnRHR and gonadotropin expression was observed in pituitary tumor with SF-1 expression than that without the expression (P < 0.01). LHRH responders showed a greater GH decrease in the octreotide test and a greater IGF-1 decrease after first-generation somatostatin ligand than LHRH nonresponders (P < 0.05). Furthermore, the proportion of hypointense pituitary tumors on T2-weighted magnetic resonance imaging and tumors with densely granulated type was higher in LHRH responders than in LHRH nonresponders, respectively (P < 0.05). No difference between the two groups was observed in either somatostatin receptor 2 or 5 expression. The increased GH response to LHRH is associated with the gonadotroph-related characteristics. This response may reflect the biological characteristics of somatotroph tumors.

LMIC-15. OUTCOMES OF PEDIATRIC MEDULLOBLASTOMA IN LOW- AND MIDDLE-INCOME COUNTRIES: A REPORT OF 330 PATIENTS FROM 8 COUNTRIES

Abstract BACKGROUND AND AIMS Reports from low-and middle-income countries (LMICs) indicate lower survival in medulloblastoma (MB), though these studies are mainly from single institutions. This multi-institutional, retrospective study aimed to analyze the outcomes for MB in 9 centers in 8 LMICs. METHODS Patients &amp;lt;18 years old with newly diagnosed MB, treated from January 2014 to December 2018 in Egypt, El Salvador, Malaysia, Mexico, Pakistan, Peru, Philippines, and Uruguay were included. Data on demographics, clinical presentation, treatment and biological characteristics were collected. Factors associated with patient outcomes were analyzed. RESULTS The study included 330 patients with a median age of 7.7 years. Of these, 49 patients (15%) were &amp;lt;3 years old and 212 (64%) were male. Eighty-eight patients (26%) had experienced symptoms for &amp;gt;3 months at diagnosis. Gross total resection was achieved in 153 (47%) patients. Sixty-three patients (19%) experienced post-operative infections. Eighty-four patients (24%) had metastatic disease at diagnosis. The histologic subtype was not specified in 98 cases (30%), and 25 patients (7%) had molecular subgroups identified. Radiotherapy was administered to 216 patients (64%). The median number of chemotherapy cycles was 8 (range 0-14). There were 64 patients (19%) who abandoned treatment, and 24 patients (7%) died due to treatment-related toxicity. The 5-year event-free survival (EFS) was 44±4%, while the 5-year overall survival was 58±4%. The 5-year EFS for patients &amp;lt;3 years was 42±9%, while 44±4% for older patients (p=0.49). The 5-year EFS for patients with metastasis was 38±7%, while it was 46±4% for patients without metastasis (p=0.13). CONCLUSIONS This large, multinational cohort of MB in LMICs describes poor outcomes, which may be attributed to delays in care, high abandonment rate, surgical complications, treatment-related mortality and a low fraction of patients receiving radiotherapy. Interventions to build care capacity can be prioritized based on these data.

Constitutional, Biological and Social Characteristics of Adolescents of Military Age with Mental Retardation

Constitutional, Biological and Social Characteristics of Adolescents of Military Age with Mental Retardation

Pathological Complete Response in Patients With Resected Pancreatic Adenocarcinoma After Preoperative Chemotherapy

Preoperative chemo(radio)therapy is increasingly used in patients with localized pancreatic adenocarcinoma, leading to pathological complete response (pCR) in a small subset of patients. However, multicenter studies with in-depth data about pCR are lacking. To investigate the incidence, outcome, and risk factors of pCR after preoperative chemo(radio)therapy. This observational, international, multicenter cohort study assessed all consecutive patients with pathology-proven localized pancreatic adenocarcinoma who underwent resection after 2 or more cycles of chemotherapy (with or without radiotherapy) in 19 centers from 8 countries (January 1, 2010, to December 31, 2018). Data collection was performed from February 1, 2020, to April 30, 2022, and analyses from January 1, 2022, to December 31, 2023. Median follow-up was 19 months. Preoperative chemotherapy (with or without radiotherapy) followed by resection. The incidence of pCR (defined as absence of vital tumor cells in the sampled pancreas specimen after resection), its association with OS from surgery, and factors associated with pCR. Factors associated with overall survival (OS) and pCR were investigated with Cox proportional hazards and logistic regression models, respectively. Overall, 1758 patients (mean [SD] age, 64 [9] years; 879 [50.0%] male) were studied. The rate of pCR was 4.8% (n = 85), and pCR was associated with OS (hazard ratio, 0.46; 95% CI, 0.26-0.83). The 1-, 3-, and 5-year OS rates were 95%, 82%, and 63% in patients with pCR vs 80%, 46%, and 30% in patients without pCR, respectively (P < .001). Factors associated with pCR included preoperative multiagent chemotherapy other than (m)FOLFIRINOX ([modified] leucovorin calcium [folinic acid], fluorouracil, irinotecan hydrochloride, and oxaliplatin) (odds ratio [OR], 0.48; 95% CI, 0.26-0.87), preoperative conventional radiotherapy (OR, 2.03; 95% CI, 1.00-4.10), preoperative stereotactic body radiotherapy (OR, 8.91; 95% CI, 4.17-19.05), radiologic response (OR, 13.00; 95% CI, 7.02-24.08), and normal(ized) serum carbohydrate antigen 19-9 after preoperative therapy (OR, 3.76; 95% CI, 1.79-7.89). This international, retrospective cohort study found that pCR occurred in 4.8% of patients with resected localized pancreatic adenocarcinoma after preoperative chemo(radio)therapy. Although pCR does not reflect cure, it is associated with improved OS, with a doubled 5-year OS of 63% compared with 30% in patients without pCR. Factors associated with pCR related to preoperative chemo(radio)therapy regimens and anatomical and biological disease response features may have implications for treatment strategies that require validation in prospective studies because they may not universally apply to all patients with pancreatic adenocarcinoma.

The Culprit behind the Mass Death of Mangroves: Egrets or Rats (Rattus losea)?

Mangroves play a crucial role in maintaining coastal ecological balance. This study focused on the impact of branch-breaking behavior on the mortality of Rhizophora stylosa in the Guangxi Shankou Mangrove Reserve. However, we found mangrove mortality in areas devoid of egret habitation, prompting a reevaluation of our research hypothesis. Further investigation suggested that nesting behavior was the primary cause of mangrove mortality. A comparison of the data from areas with egrets (Egretta garzetta, Ardea intermedia) and lesser rice-field rats (Rattus losea) activity indicated significant mechanical damage caused by rats to mangroves as the main cause of mortality. Additionally, we found that the biological characteristics of R. stylosa, particularly its stunted growth and recovery abilities after branch breaking, were key factors affecting its survival. These findings imply that rat-induced mortality may not occur in other less susceptible mangrove species. The results contradict assumptions regarding the impact of egret behavior and highlight the importance of the biological characteristics of R. stylosa. This offers fresh insights into mangrove conservation and management, emphasizing the need for ongoing observation and hypotheses verification. Future studies should explore the influence of lesser rice-field rats’ activity and the intrinsic characteristics of R. stylosa on the ecosystem’s long-term stability.

Characterising a potential nearshore nursery ground for the blackchin guitarfish (Glaucostegus cemiculus) in Ma’agan Michael, Israel

The blackchin guitarfish Glaucostegus cemiculus has suffered severe declines and regional extirpation throughout its known distributions. While this species and its relative, the common guitarfish Rhinobatos rhinobatos, have been described in the Mediterranean Sea with co-occurring habitat ranges, no research has recorded the existence or extent of these two separate populations along the Israeli coastal waters. Along a particular coast in Israel, Ma’agan Michael, fishermen have reported annual observations of juvenile guitarfish between June to November for the last forty years. Based on these citizen-based observations the main research objective is to establish whether Ma’agan Michael fulfils all three criteria from the literature by Dr Michelle Heupel, allowing it to be acknowledged as a nursery ground for G. cemiculus. The methodology built for this objective integrates biological characteristics data with the identification of a recurrent seasonal distribution. Visual surveys exhibited a significantly higher abundance in Ma’agan Michael when compared to an adjacent area (Caesarea), with 2,096 recorded observations overall. Additionally, using a species-specific modified Catch and Release protocol, a total of 492 juveniles were captured with a beach seine net. During these capturing events, individuals were morphometrically measured and sampled for future genetic analyses. Out of these, 327 specimens were also fitted for PIT tags to track recaptures in subsequent captures. The highest abundance of neonates was caught from August to September each year (2017–2019), and all individuals captured during this study were identified in the field as G. cemiculus, ranging from 20–35 cm in length (85% of captures). Many specimens had an umbilical cord scar (n = 88), with a large percentage possessing visual remains of the yolk sac. For the first time, this study provides an inter-year description of the species Glaucostegus cemiculus present along the Israeli shoreline.

DIPG-08. PROBING THE BLOOD-BRAIN-TUMOR-BARRIER WITH A MICROVASCULAR MODEL OF DIFFUSE MIDLINE GLIOMA

Abstract BACKGROUND Pediatric diffuse midline glioma (DMG) is a uniformly fatal brain tumor in children, with most patients surviving less than 12 months. Current treatment for DMG is limited, and outcomes for this tumor have not improved. The blood-brain-barrier (BBB) remains a key challenge for DMG therapeutics, preventing most drugs from entering brain tissue. Functional characterization of the blood-brain-tumor-barrier (BBTB) – the interaction between tumors and BBB vasculature – remains largely unexplored for DMG. There is a need for a preclinical model of DMG that can probe the functional, physiological, and biological properties of the BBTB in vitro as a platform to evaluate therapeutic efficacy that is representative of human physiology. METHODS To generate an in vitro model of DMG with human microvasculature (DMG-BBTB model), we co-cultured DMG neurospheres, human brain microvascular endothelial cells, human brain vascular pericytes, and human astrocytes. Cells are simultaneously seeded into microfluidic devices at varied concentrations within a fibrin matrix. Self-assembled microvascular networks are formed within 7-8 days and used for downstream functional and phenotypic assays. RESULTS Vascular morphology and solute permeability in microvascular networks are influenced by cell identity, growth pattern, and relative concentration. We show that DMG neurospheres exhibit different patterns of growth when co-cultured as uniform spheroids versus single cells in suspension. Devices representing each growth pattern are further characterized for paracellular diffusion and permeability compared to devices without DMG cells through perfusion of high molecular weight dextran. Permeability values are correlated to biologic features such as the abundance and localization of junctional proteins and transporters. CONCLUSIONS We developed a platform to evaluate the microvasculature of the DMG BBTB as a tool to develop new therapies informed by vascular biology. We probed the functional, physiological, and biological properties of the human DMG BBTB in vitro, and in ongoing work are assessing approved and experimental therapeutics.

ETMR-29. PRIMARY CNS SARCOMAS IN CHILDREN AND ADOLESCENTS: EXPERIENCE OF AN INSTITUTION

Abstract BACKGROUND Soft tissue sarcomas represent 6% of childhood cancers, less than 0.2% of CNS tumors are primary intracranial sarcomas. Their origin is pluripotential primitive mesenchymal cells. OBJECTIVE to evaluate clinical and genetic characteristics and report the experience of a rare CNS tumor. METHODS review of CNS tumors database at IOP/GRAACC/UNIFESP for the period 2008-2024, searching for all types of sarcomas that involved the CNS. RESULTS case series included 7 male, 2 female patients; average age at diagnosis 11.3 years. Supratentorial was the most common site of occurrence (66.6%), posterior fossa and intramedulary (2 and 1 cases, respectively) were found. One PF sarcoma presented as a second neoplasm after 2 years finished treatment for medulloblastoma, the other was diagnosed just after metilation. The presenting symptoms varied with tumor location, specially hemiparesis, seizure and headache. Gross total resection was achieved in 7 cases (77.7%), 1 after second look surgery. Histology and immunohistochemistry studies revealed: spinocellular sarcoma, fusocellular and myxoid sarcoma, gliosarcoma, meningeal sarcoma, Ewing sarcoma, condrosarcoma and synovial sarcoma. Work-up excluded other primary tumor origin outside CNS. Analyses for genetic characteristics were performed by Next Generation Sequencing in 6 patients (66.6%) and the following alterations were found: NRAS, TP53, JAK3, NF2, C11orf95-RELA fusion, PDGFRA. Some of these, by now, with no significant meaning for the disease. All patients underwent multimodal treatment. Chemotherapy involved mainly ICE Protocol (55.5%), but also Head Start Protocol and Ewing Sarcoma Protocol. Follow-up ranged from 13 months to 12 years, 90% of patients are alive, 2 (28.5%) dealing with endocrinal issues after focal radiotherapy. The mean overall survival was 61.4 months. CONCLUSION CNS primary sarcomas were mostly observed in the supratentorial region and in older children, with male predilection. Multimodal treatment seems to benefit patients’ outcomes. More patients and longer follow-up periods are needed to further elucidate the biological features of these tumors.

INFLUENCE OF ALUMINUM OXIDE NANOPARTICLES ON BIOLOGICAL FEATURES AND HOST HEMOCYTES OF Galleria mellonella L. (Lepidoptera: Pyralidae) WITH ITS ENDOPARASITOID Pimpla turionellae L. (Hymenoptera: Ichneumonidae)

Nanoparticles (NPs) are released directly or indirectly into nature with increased production and consumption, and their effects on insects, which occupy a large place in the ecosystem, are of interest. There is also interest in the potentially toxic effects of NPs applied to hive pests on parasitoids, or honey bees, and host-parasitoid relationships. The influence of aluminum oxide (Al2O3) NPs on the biological features of the hive pest Galleria mellonella, total counts of hemocyte, and hemocyte types; as well as on the biological features of the endoparasitoid Pimpla turionellae were investigated. The data obtained revealed that Al2O3 NPs caused a decrease in the larval, pupal, and adult development time of G. mellonella. The immature developmental time of P. turionellae was reduced. It was also demonstrated that Al2O3 NPs decreased the total counts of hemocytes in G. mellonella larvae; granulocyte, spherulocyte, oenocytoid, and prohemocyte counts decreased at all NP concentrations, while plasmatocyte counts increased. The data showed that Al2O3 NPs affected the biological properties of the hive pest model organism G. mellonella and indirectly affected its endoparasitoid P. turionellae. In addition, NPs showed a suppressive effect on cellular immune system responses, decreasing hemocyte counts. Our study results suggest that especially honey bees, honeycomb pests, and parasitoids may be negatively affected by NPs, which have increased in recent years as environmental pollutants, and that NPs may have insecticidal effects.

A hybrid structure based on silk fibroin/PVA nanofibers and alginate/gum tragacanth hydrogel embedded with cardamom extract

Hybrid structures made of natural-synthetic polymers have been interested due to high biological features combining promising physical–mechanical properties. In this research, a hybrid dressing consisting of a silk fibroin (SF)/polyvinyl alcohol (PVA) nanofibers and sodium alginate (SA)/gum tragacanth (GT) hydrogel incorporating cardamom extract as an antibacterial agent was prepared. Accordingly, SF was extracted from cocoons followed by electrospinning in blend form with PVA (SF/PVA ratio: 1:1) under the voltage of 18 kV and the distances of 15 cm. The SEM images confirmed the formation of uniform, bead free fibers with the average diameter of 199 ± 28 nm. FTIR and XRD results revealed the successful extraction of SF and preparation of mixed fibrous mats. Next, cardamom oil extract-loaded SA/GT hydrogel was prepared and the nanofibrous structure was placed on the surface of hydrogel. SEM analysis depicted the uniform morphology of hybrid structure with desirable matching between two layers. TGA analysis showed desired thermal stability. The swelling ratio was found to be 1251% after 24 h for the hybrid structure and the drug was released without any initial burst. MTT assay and cell attachment results showed favorable biocompatibility and cell proliferation on samples containing extract, and antibacterial activity values of 85.35% against S. aureus and 75% against E. coli were obtained as well. The results showed that the engineered hybrid nanofibrous-hydrogel film structure incorporating cardamom oil extract could be a promising candidate for wound healing applications and skin tissue engineering.

Machine Learning Techniques for Predicting Drug-Related Side Effects: A Scoping Review.

Drug safety relies on advanced methods for timely and accurate prediction of side effects. To tackle this requirement, this scoping review examines machine-learning approaches for predicting drug-related side effects with a particular focus on chemical, biological, and phenotypical features. This was a scoping review in which a comprehensive search was conducted in various databases from 1 January 2013 to 31 December 2023. The results showed the widespread use of Random Forest, k-nearest neighbor, and support vector machine algorithms. Ensemble methods, particularly random forest, emphasized the significance of integrating chemical and biological features in predicting drug-related side effects. This review article emphasized the significance of considering a variety of features, datasets, and machine learning algorithms for predicting drug-related side effects. Ensemble methods and Random Forest showed the best performance and combining chemical and biological features improved prediction. The results suggested that machine learning techniques have some potential to improve drug development and trials. Future work should focus on specific feature types, selection techniques, and graph-based methods for even better prediction.

ECOLOGICAL AND FAUNAL REVIEW RHOPALOCERA IN THE TERRITORY OF THE SOUTH-EASTERN PART OF THE CRIMEA

The research results provided original data on the Rhopalocera species composition, ecological and biological features, and Rhopalocera population structure, of the south-eastern part of the peninsula, which live in some open biocenoses. The role of Rhopalocera representatives in the ecosystem is twofold: representatives of the family act as pests at some stages of development, and as beneficial pollinators of flowering plants at others, which affects the development of the ecosystem as a whole. In the studied territory of the southeastern part of Crimea, 36 species of Lepidoptera were found. The studied fauna of Rhopalocera included 5 species listed in the Red Data Book of Ukraine. One species of the family Lycaenidae is listed in the Red Data Butterflies Book of Europe. Of the studied inpatients the most densely inhabited biotopes a juniper grove, meadows, and a steppe area turned out to be. By the number of species, the largest trophic group among the detected ones was the group of oligophagous. Four phenological groups were distinguished: spring-early summer, summer, late summer, and polyvoltine, of which the richest is the polyvoltine group. The peak of diversity and abundance of species occurred in the middle summer period when almost 90% of Rhopalocera species of the studied area were found.

Shell Composition Analysis of European Flat Oyster (Ostrea edulis, Linnaeus 1758) From Marmara Sea, Türkiye: Insights Into Chemical Properties

The chemical structure of Ostrea edulis (O. edulis) shells was investigated in this work. The study determined zero charge points (PZC) of Ostrea edulis shells. The shell surface charge status is indicated by the PZC value. It was found that the shell PZC value was 8.30. The shells were subjected to Energy Dispersive X-Ray Spectroscopy (EDS) analyses and scanning electron microscope (SEM) pictures. The main structure of calcium carbonate (CaCO3) is made up of carbon, oxygen, and calcium atoms, which were found in the largest quantities based on the EDS data. The structure of CaCO3 was supported by Fourier Transform Infrared Spectroscopy (FT-IR) analysis. As part of the study, X-Ray Diffraction (XRD) investigations were conducted, and it was found that the shell structures are primarily composed of an aragonite and CaCO3 mixture. As is well known, CaCO3, which makes up roughly 94% of the shell, is the primary constituent of bivalves’ shells. This research offers a thorough examination of the chemical makeup of O. edulis shells. This study is thought to serve as the foundation for further research on the biological and chemical characteristics of marine species.

Medicinal perspective of a promising scaffold – dihydropyrimidinones: A review

AbstractDihydropyrimidinones (DHMPs) are the most important pharmacophore in Medicinal Chemistry. The synthetic approach for deriving DHMPs involves the Biginelli reaction or a combination of it with other multi‐component reactions (MCRs). The scaffold has received considerable attention due to its diverse therapeutic activity. This review delves into the exploration of the biological characteristics of DHMPs, which play a pivotal role in various therapeutic areas including “anti‐inflammatory, anti‐HIV, anticancer, antitubercular, antifungal, antibacterial, antihyperglycemic, antihypertensive, anticonvulsant, antimalarial, antioxidant,” reverse transcriptase (RT) inhibitor, antispasmodic, calcium channel blockers, antiproliferative, urease inhibitor, cyclooxygenase (COX‐2), and β‐glucuronidase inhibitor activities. The insights provided in this review have the potential to aid researchers in the formulation of novel drugs, facilitating creation of more resilient, efficient, and safer therapeutic agents with reduced toxicity and minimized adverse effects.

Investigating layer-by-layer chitosan-dextran sulfate-coated mesoporous silica as a pH-sensitive drug delivery system

Mesoporous silica nanoparticles (MSNPs) coated by chitosan (CS) were shown to be a proper candidate as a carrier for drug delivery purposes. However, choosing the suitable drug-containing complexes to be applied on MSNPs-CS is of much greater importance to evaluate the possible candidate for an efficient combination of cell viability, drug release kinetics, and atherosclerosis prevention. In this regard, this study concentrates on the synthesis and assessment of coated MSNPs-CS designed for drug delivery purposes. The MSNPs are coated with polyelectrolyte complexes (PEC) composed of CS and dextran sulfate (MSNPs-CS-DX), serving as a versatile drug carrier with favorable biological characteristics. CS-DX is applied to MSNPs without requiring complex or multi-step synthesis procedures. Rosuvastatin, a cholesterol-lowering medication, is chosen for its therapeutic relevance. Additionally, CS-DX is found to relatively impede the uptake of low-density lipoproteins (LDLs) by macrophages, enhancing their potential therapeutic utility. FTIR pattern, FESEM, and TEM images prove MSNPs-CS-DX formation. DLS measurement demonstrates the average particle size of 110 nm for MSNPs, with the combined thickness of CS and DX layers ranging from 10 to 15 nm. BET test is carried out to evaluate the pore size and porosity of structure, showing outstanding results that cause an entrapment efficiency of 57% for MSNPs-CS-DX. Furthermore, the findings demonstrate the pH sensitivity of MSNPs-CS-DX on drug release kinetics. Notably, the CS-DX layer exhibits a significant enhancement in cell viability of human umbilical vein endothelial cells (HUVEC) by approximately 24% within a 24 h timeframe compared to MSNPs lacking CS-DX.Graphical

Immunotherapy for pediatric low-grade gliomas.

Pediatric low-grade gliomas (pLGGs) are the most common brain tumor types affecting children. Although gross-total resection remains the treatment of choice, many tumors are not amenable to complete removal, because they either involve midline structures, such as the optic chiasm or hypothalamus, and are not conducive to aggressive resection, or have diffuse biological features and blend with the surrounding brain. Historically, radiation therapy was used as the second-line option for disease control, but with the recognition that this often led to adverse long-term sequelae, particularly in young children, conventional chemotherapy assumed a greater role in initial therapy for unresectable tumors. A variety of agents demonstrated activity, but long-term disease control was suboptimal, with more than 50% of tumors exhibiting disease progression within 5 years. More recently, it has been recognized that a high percentage of these tumors in children exhibit constitutive activation of the mitogen-activated protein kinase (MAPK) pathway because of BRAF translocations or mutations, NFI mutations, or a host of other anomalies that converged on MAPK. This led to phase 1, 2, and 3 trials that explored the activity of blocking this signaling pathway, and the efficacy of this approach compared to conventional chemotherapy. Despite initial promise of these strategies, not all children tolerate this therapy, and many tumors resume growth once MAPK inhibition is stopped, raising concern that long-term and potentially life-long treatment will be required to maintain tumor control, even among responders. This observation has led to interest in other treatments, such as immunotherapy, that may delay or avoid the need for additional treatments. This chapter will summarize the place of immunotherapy in the current armamentarium for these tumors and discuss prior results and future options to improve disease control, with a focus on our prior efforts and experience in this field.

Synthesis and biological characterization of an orally bioavailable lactate dehydrogenase-A inhibitor against pancreatic cancer

Lactate dehydrogenase-A (LDHA) is the major isoform of lactate dehydrogenases (LDH) that is overexpressed and linked to poor survival in pancreatic ductal adenocarcinoma (PDAC). Despite some progress, current LDH inhibitors have poor structural and physicochemical properties or exhibit unfavorable pharmacokinetics that have hampered their development. The present study reports the synthesis and biological evaluation of a novel class of LDHA inhibitors comprising a succinic acid monoamide motif. Compounds 6 and 21 are structurally related analogs that demonstrated potent inhibition of LDHA with IC50s of 46 nM and 72 nM, respectively. We solved cocrystal structures of compound 21-bound to LDHA that showed that the compound binds to a distinct allosteric site between the two subunits of the LDHA tetramer. Inhibition of LDHA correlated with reduced lactate production and reduction of glycolysis in MIA PaCa-2 pancreatic cancer cells. The lead compounds inhibit the proliferation of human pancreatic cancer cell lines and patient-derived 3D organoids and exhibit a synergistic cytotoxic effect with the OXPHOS inhibitor phenformin. Unlike current LDHA inhibitors, 6 and 21 have appropriate pharmacokinetics and ligand efficiency metrics, exhibit up to 73% oral bioavailability, and a cumulative half-life greater than 4 h in mice.

Wild goose in the traditional worldview of the Buryats

The purpose of this study is to identify the image of the wild goose in the traditional worldview of the Buryats. The timeframe of this research covers the end of the 19th — middle of the 20th c., the period when the Buryats overall retained their set of mythological views. Geographically, the survey is focused on south-eastern Siberia, which includes ethnic Buryatia. The research is based on a variety of sources, including folklore, linguistic and ethnographic information. The structural-semiotic method has been chosen as the main technique of study, which allows determination of the symbolism that conveys the ideas about wild goose. It has been revealed that in minor genres of the Buryat folklore, the feminine nature of the wild goose is emphasized, and their anthroponymy mani-fests its gender differences. It has been found that, for the Buryats, the individual biological and behavioral char-acteristics of the goose were of a particular importance. It has also been determined that natural rhythms (the start of spring and the middle of autumn) were associated with the wild goose, as well as the first snowfall. At the same time, significant importance was attributed to its cry. Its image symbolized long distances and time. The motive of shapeshifting was also linked to it. This bird, both in shamanic and Buddhist traditions, was considered to be an assistant to the deity (the supreme celestial being among shamanists, and the White Elder among Bud-dhists). In the Buryat epics, it was endowed with a negative connotation. According to the traditional perceptions of some of the Cis-Baikal Buryats, the wild goose had a sacred status, and the interchangeability of images of a goose and another sacred bird — a swan — has been noted. The goose (precisely, the female goose) acted as a totem for a number of Cis-Baikal kins.

The Pathogenic Mechanism of Enterocytozoon hepatopenaei in Litopenaeus vannamei.

Enterocytozoon hepatopenaei (EHP) is a parasite in shrimp farming. EHP mainly parasitizes the hepatopancreas of shrimp, causing slow growth, which severely restricts the economic income of shrimp farmers. To explore the pathogenic mechanism of EHP, the host subcellular construction, molecular biological characteristics, and mitochondrial condition of Litopenaeus vannamei were identified using transmission electron microscopy (TEM), real-time qPCR, an enzyme assay, and flow cytometry. The results showed that EHP spores, approximately 1 μm in size, were located on the cytoplasm of the hepatopancreas. The number of mitochondria increased significantly, and mitochondria morphology showed a condensed state in the high-concentration EHP-infected shrimp by TEM observation. In addition, there were some changes in mitochondrial potential, but apoptosis was not significantly different in the infected shrimp. The qPCR results showed that the gene expression levels of hexokinase and pyruvate kinase related to energy metabolism were both upregulated in the diseased L. vannamei. Enzymatic activity showed hexokinase and lactate dehydrogenase were significantly increased in the shrimp infected with EHP, indicating EHP infection can increase the glycolysis process and decrease the oxidative phosphorylation process of L. vannamei. Previous transcriptomic data analysis results also support this conclusion.