bluuebunny/crossref_metadata_2025 huggingface dataset:
The role of Otx2 in organizing the anterior patterning in mouse.
Authors: Simeone A , Acampora D
Published: February 2025

Understanding the molecular mechanism controlling induction and maintenance of signals required for specifying anterior territory (forebrain and midbrain) of the central nervous system is a major task of molecular embryology. The current view indicates that in mouse, early specification of the anterior patterning is established at the beginning of gastrulation by the anterior visceral endoderm, while maintenance and refinement of the early specification is under the control of epiblast-derived tissues corresponding to the axial mesendoderm and rostral neuroectoderm. In vertebrates a remarkable amount of data has been collected on the role of genes contributing to brain morphogenesis. Among these genes,the orthodenticle group is defined bythe Drosophila orthodenticle and the vertebrate Otx1 and Otx2 genes, which contain a bicoid-like homeodomain. Mouse models and chimera experiments have provided strong evidence that Otx2 plays an important role in the specification and maintenance of the rostral neuroectoderm destined to become forebrain and midbrain. In evolutionary terms, some of these findings lead us to hypothesize a fascinating and crucial contribution of the Otx genes to the genetic program underlying the establishment of the mammalian brain.
Otx2 and HNF3beta genetically interact in anterior patterning.
Authors: Jin O , Harpal K , Ang S L , Rossant J
Published: February 2025

Patterning the developing nervous system in the mouse has been proposed to depend on two separate sources of signals, the anterior visceral endoderm (AVE) and the node or organizer. Mutation of the winged-helix gene HNF3beta leads to loss of the node and its derivatives, while mutation of the homeobox gene Otx2 results in loss of head structures, apparently at least partially because of defects in the AVE. To investigate the potential genetic interactions between the two signaling centers, we crossed Otx2+/- and HNF3beta+/- mice and found that very few Otx2+/-;HNF3beta+/- double heterozygous mutants survived to weaning. Normal Mendelian ratios of genotypes were observed during gestation, but more than half the double heterozygotes displayed a severe anterior patterning phenotype that would be incompatible with postnatal survival. The phenotype was characterized by varying degrees of holoprosencephaly, cyclopia with proboscis-like structures, and anterior forebrain truncations. Regional marker analysis revealed that ventral forebrain structures of Otx2+/-;HNF3beta+/- mutant embryos were most severely affected. Shh expression was completely absent in the anterior region of Otx2+/-;HNF3beta+/- embryos, suggesting that Otx2 and HNF3beta genetically interact, directly or indirectly, to regulate Shh expression in the anterior midline. In addition, the forebrain truncations suggest an involvement of both genes in anterior patterning, through their overlapping expression domains in either the AVE and/or the prechordal mesoderm.
Spemann's heritage in Finnish developmental biology.
Authors: Saxen L
Published: February 2025

The Finnish school of developmental biology can be considered a direct descendant of Spemann's school as both the original technology and the fundamental problems were introduced into Finland by Gunnar Ekman (1883-1937) who had worked for extended periods in Germany. After his early death, the work was continued by Sulo Toivonen (1909-1995), and until 1968 the group explored the mechanisms of primary induction and the subsequent segregation of the central nervous system. The extensive investigations led to the formulation of the "double-gradient" hypothesis and ultimately to its experimental vindication.
Kidneys in Meckel's syndrome as a model of abnormal renal differentiation.
Authors: Rapola J
Published: February 2025

Kidneys of nine human fetuses of 16-22 weeks of gestational age with Meckel's syndrome were studied. All kidneys were grossly enlarged and cystic. The morphological picture is appreciably different form the kidneys of full term infants with the same syndrome. All kidneys showed distinct subcapsular nephrogenic zone from which the cysts arise. The cyst wall retains characteristics that recall its origins from preformed nephrons and collecting ducts, as can be demonstrated histologically and with lectin and antibody markers. Studies on abnormal fetal kidneys when combined with segment-specific molecular markers of the nephron are invaluable in unraveling the pathogenesis of the various types of human cystic renal diseases.
Basement membrane matrices in mouse embryogenesis, teratocarcinoma differentiation and in neuromuscular maturation.
Authors: Leivo I , Wartiovaara J
Published: February 2025

In this paper we discuss studies on basement membrane and interstitial matrix molecules in early development and teratocarcinoma differentiation. In the early embryo a compartmentalization of newly formed cell types takes place immediately by formation of basement membranes. The stage-specific developmental appearance of extracellular matrix molecules such as type IV collagen, laminin, entactin, fibronectin and proteoglycans seems to reflect a diversified role of extracellular matrices already in the earliest stages of development. In teratocarcinoma cultures the appearance and composition of extracellular matrices during the differentiation of endoderm cells closely resembles that found in the early embryo. Also in this respect the teratocarcinoma system can be used as a model for studies on early development. In later developmental phenomena other matrix molecules can also be of importance. Merosin, a novel tissue-specific basement membrane-associated protein that appears during muscle and nerve maturation is an example of such molecules.
Macronucleus structure and macronucleus development in hypotrichous ciliates.
Authors: Lipps H J , Eder C
Published: February 2025

In the course of macronuclear development of the hypotrichous ciliates all genetic information not required for normal growth of the cell is removed from the new macronucleus. This differentiation process involves DNA-splicing, excision of transposons, DNA-fragmentation, selective gene amplification and telomere addition. Since many of the processes observed during macronuclear development, such as DNA-transposition, DNA-rearrangement or selective DNA-amplification, may occur in differentiating cells of higher organisms, this biological system provides an unusual opportunity to study the ways in which DNA-sequences can be manipulated in a differentiating cell.
Muscle development and attachment to the epidermis is accompanied by expression of beta 3 and beta 1 tubulin isotypes, respectively.
Authors: Buttgereit D , Paululat A , Renkawitz-Pohl R
Published: February 2025

In Drosophila beta tubulins are encoded by a small gene family whose members are differentially expressed in a highly cell and tissue specific manner. Here we focus on the expression of the beta 3 tubulin isotype during mesoderm differentiation and beta 1 tubulin expression in the apodemes during embryonic development. The beta 3 tubulin isotype is first detectable at the extended germband stage shortly before the separation of somatic and visceral derivatives. Comparing the distribution of the beta 3 mRNA and the beta 3 isotype shows that the transcription of the beta 3 tubulin gene is cell type specifically repressed during differentiation of individual mesodermal derivatives, from which the dorsal vessel remains transcriptionally active until shortly before hatching. In contrast the beta 3 tubulin protein is detectable in all mesodermal derivatives. The beta 3 tubulin is an excellent marker to study mesoderm differentiation on a regulatory and cellular level using both genetics and molecular biology. In the visceral mesoderm, the expression of the beta 3 tubulin gene is regulated by homeotic gene products, while other transactivators regulate expression in the dorsal vessel and the body wall musculature. In the somatic mesoderm, the beta 3 tubulin allows to visualize myotube formation and insertion into the epidermis. This contact to the epidermal attachment sites (apodemes) induces beta 1 tubulin expression, as can be seen in double staining experiments. We determined a 14bp cis-regulatory enhancer element guiding expression of the beta 1 tubulin gene in these attachment sites. Using the beta 1 and beta 3 tubulin isotypes as markers we started to isolate mutants which are disturbed in muscle formation.
Larval and imaginal pathways in early development of Drosophila.
Authors: Harbecke R , Meise M , Holz A , Klapper R , Naffin E , Nordhoff V , Janning W
Published: February 2025

In holometabolous development, higher insects have two different life forms, the larva and the imago. Both larval and imaginal cells are derived from cells of the blastoderm stage. After the final embryonic wave of mitosis, however, only the imaginal cells remain diploid, proliferate massively and do not differentiate until metamorphosis. The separation of these two pathways was described by many authors as a fundamental process that must take place at a very early stage of development, most probably the blastoderm stage. Mainly by using single cell transplantations at the blastoderm or early gastrula stages, respectively, we found common cell lineages between larval and imaginal structures by clones overlapping in the ectoderm (i.e. larval epidermal cells and imaginal discs within a segment, or larval and imaginal salivary gland cells), the mesoderm (i.e. larval somatic muscles and adepithelial cells), and the endoderm (i.e. larval and imaginal midgut cells). From these findings we conclude that it seems to be a principle in Drosophila embryogenesis that the separation of larval and imaginal pathways is postponed to a later developmental stage.
Regulation and function of the tissue-specific transcription factor HNF1 alpha (LFB1) during Xenopus development.
Authors: Weber H , Strandmann E P , Holewa B , Bartkowski S , Zapp D , Zoidl C , Ryffel G U
Published: February 2025

We review the data available on the structure, developmental appearance and embryonic regulation of the tissue-specific transcription factor HNF1 alpha (LFB1) in Xenopus. The expression of the HNF1 alpha gene starts early in embryogenesis shortly after mid-blastula transition and the protein accumulates in the region of the embryo where liver, pronephros and gut--tissues that contain HNF1 alpha in the adult--are developing. The cofactor DCoH, known to stabilize dimer formation of HNF1 alpha, is present as a maternal factor in the egg and has a partially distinct tissue distribution compared to HNF1 alpha. This implies that DCoH does not only modulate HNF1 alpha dimerization but may also cooperate with other transcription factors. By injecting HNF1 alpha promoter CAT constructs into fertilized Xenopus eggs we obtained activation of the injected gene restricted to the region of the developing larvae expressing endogenous HNF1 alpha. Deletion analysis allowed to define the OZ-element that is essential for embryonic activation. This element also occurs in other promoters activated at mid-blastula transition in the embryo and interacts with the maternal factor OZ-1. As the HNF1 alpha promoter also contains functional binding sites for HNF4 and HNF1, we postulate that all of these transcription factors contribute to the cascade leading to proper embryonic activation of the HNF1 alpha gene.
Metamorphosis and pattern formation in Hydractinia echinata, a colonial hydroid.
Authors: Walther M , Ulrich R , Kroiher M , Berking S
Published: February 2025

There are several reasons why Hydractinia echinata Hydrozoa, Cnidaria) is excellently suited to study developmental processes. In the laboratory fertilization takes place every morning in the seawater in thousands of eggs. Cleavage starting synchronously leads to a ciliated planula larva within 2 to 3 days. Onset of metamorphosis from the larval to the polyp stage must be triggered externally. There are several agents known to induce or to interfere with induction of metamorphosis thus allowing access to the biochemical basis of this process. The pattern of the resultant polyp can be influenced by certain treatments during the process of metamorphosis allowing access to a process of proportioning. The colony develops by elongation of hollow tubes at the base of the polyps, termed stolons on which in more or less regular intervals new polyps emerge. Two (main) types of polyps are formed allowing to study spacing by lateral inhibition and lateral dependence of each other. In the present paper current data and hypotheses concerning all these topics are discussed.
Signals and signal-transduction systems in the control of development in Hydra and Hydractinia.
Authors: Hassel M , Leitz T , Muller W A
Published: February 2025

Pattern control in Hydra has traditionally been assigned to the determining influence of morphogens and neuropeptides. However, at present, arachidonic acid and its derivative 12-S-HETE are the only identified, potential signal molecules known to promote head and bud formation. More potent factors might exist but are not yet identified. Nonetheless, it is possible to evoke the development of an almost unlimited number of supernumerary head structures and to induce ectopic foot formation by interference with the PI-PKC signal transducing system. Such an interference can also rescue the regeneration-deficient mutant reg-16. Regarding signals in the development of Hydractinia, metamorphosis is induced by an external key stimulus, i.e. a lipid derived from environmental bacteria. The reception of this stimulus involves PKC-mediated responses. Upon its reception, a neuropeptide is released as an internal, synchronising signal. Members of the novel LWamide family of peptides appear to represent this internal signal. In postmetamorphic development, a glycoprotein SIF serves as an inducer of stolon formation.
Checkpoints in the life-cycle of Cassiopea spp.: control of metagenesis and metamorphosis in a tropical jellyfish.
Authors: Hofmann D K , Fitt W K , Fleck J
Published: February 2025

Experimental data reveal that most, if not all, major events in the metagenetic life-cycle of Cassiopea spp. at these checkpoints depend on the interaction with specific biotic and physical cues. For medusa formation within a permissive temperature range by monodisk strobilation of the polyp, the presence of endosymbiotic dinoflagellates is indispensable. The priming effect of the algal symbionts is not primarily coupled with photosynthetic activity, but was found to be enhanced in the light. Budding of larva-like propagules by the polyp, however, is independent from such zooxanthellae. On the other hand the budding rate is influenced by various rearing conditions. Exogenous chemical cues control settlement and metamorphosis into scyphopolyps of both sexually produced planula larvae and asexual propagules. In laboratory experiments two classes of metamorphosis inducing compounds have been detected: a family of oligopeptides, featuring a proline-residue next to the carboxyterminal amino acid, and several phorbol esters. Using the peptide 14C-DNS-GPGGPA, induction of metamorphosis has been shown to be receptor-mediated. Furthermore, activation of protein kinase C, a key enzyme within the inositolphospholipid-signalling pathway appears to be involved in initiating metamorphosis. In mangrove habitats of Cassiopea spp. planula larvae specifically settle and metamorphose on submerged, deteriorating mangrove leaves from which biologically active fractions have been isolated. The chemical characterisation and comparison of these compounds from the natural environment with the properties and mode of action of oligopeptide inducers is in progress.
Malformations after radiation exposure of preimplantation stages.
Authors: Streffer C , Muller W U
Published: February 2025

Our studies have shown that, contrary to the opinion in most textbooks, it is possible to increase the number of malformed fetuses in one of our mouse strains (originally "Heiligenberger Stamm", meanwhile HLG/Zte) by radiation exposure of zygotes or of subsequent preimplantation stages. The malformation affected most pronouncedly is gastroschisis, a defect occurring at a frequency of 1 to 4% in the controls. The observed increase is strain specific (C57Bl mice or (HLGxC57Bl)F1 hybrids do not react in the same way), it is accompanied by an increased frequency of chromosomal aberrations in skin fibroblasts and of modified protein patterns in liver, kidney, and skin cells of day 19 fetuses. The most probable explanation seems to be the assumption that radiation exposure of preimplantation stages increases a defect with a genetic predisposition in a specific way and labelizes the genome of subsequent cell generations making these cells more susceptible for noxes acting on the fetus.
Organization and expression of the developmentally regulated H1(o) histone gene in vertebrates.
Authors: Doenecke D , Alonso A
Published: February 2025

The H1 class of histones comprises several main-type, S-phase dependent isoforms and, in addition, a sperm-specific H1t and a peculiar subtype, H1 zero, which is confined to highly differentiated cells. In contrast to main type histone genes, the H1 zero gene expression does not strictly depend on DNA replication. Also in contrast to the other H1 subtype genes, the mammalian H1 zero gene is not included in a histone gene cluster and its mRNA differs in structure, size and mode of processing from other histone mRNAs. The regulation of expression of the H1 zero gene varies from main type H1 genes in several respects. This is manifested in the promoter structure which contains sequence elements that are also found in main type H1 promoters, but also shows regulatory motifs which appear to be involved in a developmental regulation of the H1 zero gene, such as a retinoic acid receptor binding site, which has been described in the mammalian H1 zero gene promoter.
Fibroblast growth factor and its implications for developing and regenerating neurons.
Authors: Grothe C , Wewetzer K
Published: February 2025

FGF is a multifunctional heparin-binding protein which was characterized by its mitogenic and angiogenic action outside the nervous system. Recent data confirm this multifunctionality also with regard to the nervous system. The distribution of FGF and its receptors seems not to be in agreement with the idea of a single function for one population but argues for a more complex action, which might be dependent on the development stage and cell type. FGF and its receptors are widely distributed in the nervous system. In brainstem and spinal cord motoneurons and in sensory ganglia the FGF-2 staining pattern is developmentally regulated suggesting a functional change during embryonic and postnatal development. In addition, after nerve lesion the FGF-2 expression is altered in sensory and motoneurons. Administration of FGF-2 reveals trophic effects on survival and transmitter metabolism in vivo and in vitro. According to a more general neurotrophic factor concept, a physiological role of FGF for distinct neuron populations during development is likely. In the motor system, for example, FGF could act synergistically with certain neurotrophins, CNTF, or other non-identified co-factors. In the sensory system, a possible non-neurotrophic role for at least postnatal and adult sensory neurons has to be further addressed in the future. In order to further define and characterize the actions of the FGFs a mapping of the different family members and their respective receptor molecules during development and in the adult has to be done.
Halaman Belakang
Authors: Editor Editor
Published: February 2025

Cover Belakang
Expression of CD44v6 Correlates with Cell Proliferation and Cellular Atypia in Urothelial Carcinoma Cell Lines 5637 and HT1197
Authors: Kuncová J. , Kostrouch Z. , Viale M. , Revoltella R. , Mandys Václav
Published: February 2025

CD44 comprises a family of membrane adhesion molecules encoded by a single gene and diversified by alternative splicing and extensive posttranslational modifications. Alterations of CD44 expression patterns are linked to tumour invasion and formation of metastases. However, CD44 expression and its relation to the biological properties of tumours vary depending on the tumour type and origin. In transitional cell carcinoma of the urinary bladder, low CD44 expression is linked to enhanced tumour aggressiveness. We studied CD44 expression in two urothelial cancer cell lines, HT1197 and 5637. CD44s and a v6 variable exon-containing splice variants were detected in both cell lines by reverse transcription-PCR and by commercially available monoclonal antibodies. In both cell lines, Western blot analysis detected immunoreactive proteins with approximate sizes 70–85 kD, 95–110 kD, and 120–140 kD with CD44v6 antibody and weak bands with size 70–98 kD with CD44s antibody. At the cellular level, the pattern of CD44 immunoreactivity correlated with a lower level of cell differentiation and a higher degree of cell proliferation. In HT1197 cells, the CD44v6 was detected predominantly in small proliferating cells and in large multinuclear atypical cells. CD44s and CD44v6 displayed low immunoreactivity in HT1197 cells with a higher degree of epithelial differentiation. The 5637 cells expressed CD44v6 strongly and CD44s weakly. We conclude that CD44v6 expression correlates with a higher proliferative activity and with a stem cell-like phenotype in both cell lines and with cellular atypia in HT1197 cells.
Immunotherapeutic Efficacy of Vaccines Generated by Fusion of Dendritic Cells and HPV16-Associated Tumour Cells
Authors: Šímová Jana , Bubeník J. , Bieblová J. , Indrová M. , Jandlová T.
Published: February 2025

Utilization of vaccines generated by fusion of dendritic cells and tumour cells is a promising approach to tumour immunotherapy. We have examined the therapeutic efficacy of vaccines generated by fusion of HPV16-associated tumour cells TC-1 with syngeneic and allogeneic dendritic cells. Locally administered hybrid cells generated by fusion of MHC class I+ TC-1 cells and syngeneic DC inhibited the growth of MHC class I+ TC-1 tumours, but not the growth of MHC class I- TC-1/A9-derived tumours. The growth of TC-1 tumours was also inhibited by hybrids generated by fusion of TC-1 cells and allogeneic DC. The therapeutic efficacy was enhanced by co-administration of the vaccine with synthetic immunostimulatory ODN CpG 1826.
Effect of Protein Supplement Source on Porcine Oocyte Maturation and Subsequent Embryonic Development after Parthenogenetic Activation
Authors: Krylov Vladimír , Křen R. , Okada K. , Vacková I. , Tlapáková T. , Fulka J.
Published: February 2025

The aim of this study was to compare the effect of purified GPBoS and commonly used FCS on porcine oocyte maturation and subsequent embryonic development after their parthenogenetic activation. COCs were obtained from dissected follicles and cultured for 18, 24, 30, 36, 42 and 48 h in M-199 medium either with GPBoS or FCS. After 24 h with GPBoS, 91% of oocytes reached MI stage while in the medium supplemented with FCS, only 29% of oocytes reached the same stage (P < 0.05). The majority of oocytes from the FCS group (61%) reached MI stage approximately 6 h later. In the time periods between 36 to 48 h both groups of oocytes reached the same stage of maturation. After 48 h of culture the oocytes with extruded polar bodies were activated by a single electric pulse and then cultured with 4 mM 6-DMAP. Activated oocytes were cultured in PZM-3 medium supplemented with 3 mg/ml of BSA. After 7 days, the development and the quality of embryos were evaluated. The results showed that the maturation of oocytes in the presence of GPBoS significantly increased their subsequent developmental ability when compared with FCS supplementation (27% vs. 19% of blastocysts, P < 0.05). However, differential staining revealed that once blastocysts were formed in either group, they had the same total cell number (40 vs. 41) and also the ICM/total cell ratio (0.27 vs. 0.29).
Study of total phenolic and flavonoid contents, antioxidant, and antibacterial properties of Zanthoxylum chalybeum and Euphorbia ingens: Medicinal plants from Malawi
Authors: Kumwenda F D , Sumani J , Jere W , Namandwa B , Nyirenda K K , Mwatseteza J
Published: February 2025

This study investigated the chemical composition, antioxidant, and antibacterial activities of two medicinal plants from Malawi: Zanthoxylum chalybeum and Euphorbia ingens. Plant extracts were obtained sequentially macerating the root powder with n-hexane, dichloromethane, ethyl acetate, methanol, and water. Total phenolics and flavonoids were determined by the Folin-Ciocalteau and aluminum chloride methods, respectively, while antioxidant activity was assessed by DPPH and FRAP assays. The antibacterial activity against Staphylococcus aureus and Pseudomonas aeruginosa was evaluated using the disc diffusion method. Flavonoids ranged from 13.40 to 30.27 mg/g for Z. chalybeum extracts and 21.76 to 66.27 mg/g for E. ingens, with the highest amounts in ethyl acetate extracts of both plants. Both plants had the highest amounts of total phenolics in methanol extracts, with Z. chalybeum and E. ingens exhibiting 284.85 and 351.59 mg/g, respectively. The DPPH radical scavenging activity test showed that E. ingens, with IC50 values of 11.28 and 12.85 ?g/mL for the aqueous and methanol extracts, respectively, is a stronger antioxidant than Z. chalybeum. The FRAP activity was highest in methanol extracts for E. ingens (2831.77±179.02 mg/g) and Z. chalybeum (799.15±32.43 mg/g). Both plants exhibited more potent antibacterial activity against S. aureus compared to P. aeruginosa. Dichloromethane and ethyl acetate extracts of Z. chalybeum showed significant activity against S. aureus with MIC values of 1.56 mg/mL, demonstrating their strong inhibitory potential. The study has revealed that both E. ingens and Z. chalybeum roots would be excellent natural antioxidants and antibacterial agents.
Comprehensive assessment of the long-term stressful event impacts on the mental health of medical students
Authors: Ogorenko V. V. , Kokashynskyi V. O. , Shornikov A. V. , Brydun O. Ye. , Khliebnykov M. O.
Published: February 2025

The aim of the study was to examine the impact of long-term exposure to stressful events (the COVID-19 pandemic and prolonged martial law) on the mental health of medical students.
Material and methods. The study was conducted among 4th–5th-year education applicants at Dnipro State Medical University (DSMU), specialty 222 “Medicine”. Group 1 consisted of 67 students examined in 2019, and Group 2 comprised 61 students examined in 2024. Clinical-anamnestic, clinical-psychopathological and psychodiagnostic examinations were conducted. The following psychometric scales were used: PHQ-9 health questionnaire, Dutch Eating Behavior Questionnaire (DEBQ), State-Trait Anxiety Inventory (STAI; C. D. Spielberger, Y. L. Hanin), Michigan Alcoholism Screening Test (MAST), Quality of Life Enjoyment and Satisfaction Questionnaire (Q-LES-Q).
Results. The data obtained have shown a statistically significant difference in alcohol screening indicators between the two groups of examinees. According to the questionnaire, students surveyed in 2024 have reported consuming less alcohol. In general, the findings from both groups have revealed normal weight, restrained and emotional eating behavior (EB) traits, absence of alcoholism, and a moderate level of the quality of life index (QOL). However, mild depression, a tendency towards externalizing EB, and a moderate level of trait anxiety have been found among the examinees. The statistical analysis results have shown a weak effect of high trait anxiety (0.135) on the development of clinically significant depression. An analysis of relative risks and odds ratios has found increased relative risks and odds ratios for poor QOL indices and clinically significant depression among individuals examined in 2024 based on a several-fold increase in these values for the indicator “High trait anxiety”.
Conclusions. Our study has demonstrated an increased strength of associations between factors (emotional eating, high trait anxiety) that influenced the onset of clinically significant depression and an increase in relative risks and odds ratios of its development among the students surveyed in 2024. A small effect of long-term stressful events (the COVID-19 pandemic and prolonged martial law) on the factors of clinically significant depression has been found. In such extreme conditions, medical students of DSMU have demonstrated a high level of stress resilience in the conditions of long-term exposure to extreme stressful events, which was confirmed by our study results revealing no significant deterioration in the mental health and quality of life in 2024 student sample compared to 2019 one.
Expert evaluation of priority areas for implementation of medical and pharmaceutical technologies in Ukraine
Authors: Babenko M. M. , Kosiachenko K. L.
Published: February 2025

Aim. To analyze survey results of healthcare (НС) professionals on the status, problems and prospects of implementing medical and pharmaceutical technologies in Ukraine and their proper appraisal.
Materials and methods. A comprehensive sociological study was conducted via an online survey using Google forms (September – December 2023). Two questionnaires were developed and tested for this purpose, one for public administration professionals and another for health technology assessment (HTA) specialists. Respondents were selected by purposive sampling based on their managerial experience, education, and professional qualifications. In total, 164 НС system managers of different levels and 77 HTA specialists were enrolled in the study. The methods of system analysis, mathematical and statistical, generalization, comparison, descriptive, and graphical were used to process and interpret the results.
Results. Based on current scientific concepts and regulatory requirements, medical and pharmaceutical technologies include various methods, procedures, systems or tools applied in the field of HC for treatment, diagnosis, prevention, medical rehabilitation and palliative care. The WHO also defines HC technologies as public health measures and interventions at the population level (such as vaccination, screening), targeted programs, and treatment standards (protocols, guidelines). The modern НТА methodology as a scientific and practical concept is now developing quite dynamically in the world and has specific features of implementation in different countries.
Conclusions. Since НТА is an internationally recognized tool to support effective management decision-making, a comparison between НТА specialist and НС manager opinions on the status, problems and prospects of НТА implementation in Ukraine has been important in the study. The respondents have reported the formation of a professional environment, improvement of legislation, international cooperation, infrastructure development and capacity building as the most probable scenario for the НТА implementation in Ukraine.
Clinical characteristics and management of post-myocardial infarction patients with stable angina in the outpatient practice of Ukrainian cardiologists (GO-OD study)
Authors: Parkhomenko O. M. , Kolesnyk M. Yu. , Koval O. A. , Tykhonova S. A.
Published: February 2025

Aim. To identify the clinical and anamnestic characteristics and features of the stable angina management in patients with a history of myocardial infarction (MI) in the actual outpatient practice of Ukrainian cardiologists in order to determine the follow-up activities for optimizing and individualizing the treatment of this patient cohort.
Materials and methods. The non-interventional observational multicenter prospective study GO-OD enrolled 1529 patients with coronary artery disease, stable angina, 39.7 % of whom had a history of MI. The follow-up period for the study participants was 3 months. Physicians were instructed to continue monitoring and treatment of patients in accordance with routine practice and international guidelines. No additional diagnostic or monitoring procedures were performed. However, physicians could adjust therapy and provide recommendations for lifestyle modification.
Results. Among post-infarction patients, the proportion of young people, active smokers and men was significantly higher (p < 0.001). A positive family history of MI in first-degree relatives or sudden death in the patient’s father before 55 years of age have been identified to be more common in MI patients (p < 0.05), a positive family history of stroke has been found in the group of patients without MI (p < 0.001). Patients with MI had an average of 6 anginal attacks per week, and the need for short-acting nitroglycerin to relieve attacks was significantly higher than that in patients without MI. PCI was used more often for MI patients within up to 3 years post-MI, the proportion of CABG gained prevalence among patients over 3 years after MI. At the time of study enrollment, the patients mostly used beta-blockers, trimetazidine was the second most often prescribed. When optimizing antianginal therapy, trimetazidine therapy underwent the greatest modifications, the proportion of patients taking beta-blockers and calcium antagonists also increased, which resulted in a significant symptom alleviation in patients. Recommended highly intensive statin therapy was prescribed only to 44.2 % of patients and none of the patients received combined lipid-lowering therapy.
Conclusions. Controlling the modifiable risk factors remains unsatisfactory among Ukrainian outpatients with angina and a history of MI. Despite prior coronary revascularization procedures, significant symptomatology in patients with angina and MI has been detected. Low therapy adherence has been documented in most patients. Fewer than half of patients with a history of MI receive the required doses of statins. Pharmacological therapy optimization through adjustment of hypolipidemic and antianginal medication dosages, and the inclusion of original trimetazidine at a dose of 80 mg once a day have resulted in a significantly reduced frequency of anginal attacks and improved quality of patients’ life.
Studying associative relations between left ventricular dysfunction and heart failure development in patients with acute coronary syndrome and clinical manifestation of COVID-19
Authors: Bondarets D. V. , Rudenko K. V.
Published: February 2025

The aim of the work: to determine associative relations between left ventricular dysfunction and heart failure development in patients with acute coronary syndrome and COVID-19.
Materials and methods. Patients with acute coronary syndrome and manifestation of COVID-19 were included in the study (n = 100). The material for the analysis was the data of echocardiography and coronary angiography. The study participants underwent myocardial revascularization.
Results. It has been found that ejection fraction before reperfusion was 2.4 % higher in the main group (p ≥ 0.05), and it was increased by an average of 1.2 % (p ≥ 0.05) after reperfusion. In the comparison group, the mean value of ejection fraction did not differ before and after reperfusion. A comparative analysis of ejection fraction after reperfusion has shown its increase by an average of 52.0 % in the main group and by 48.0 % in the comparison group, indicating the treatment effectiveness. The determined OR coefficients have indicated a 0.85-fold reduced heart failure risk in the comparison group (OR = 0.85; 95 % CI: 0.36–2.01, p = 0.8). A 0.78 times decreased heart failure risk has been revealed in patients with unchanged ejection fraction after reperfusion in the comparison group (OR = 0.78; 95 % CI: 0.26–2.31, p = 0.8), while it has been shown to be 1.47 times higher in those with decreased ejection fraction (OR = 1.47; 95 % CI: 0.57–3.79, p = 0.5).
Conclusions. The determined OR coefficients have demonstrated associative relations between a reduction in the heart failure risk in single-vessel (OR = 0.67; 95 % CI: 0.06–7.31, p = 0.5), two-vessel (OR = 0.40; 95 % CI: 0.01–10.17, p = 0.5) and multivessel (OR = 0.79; 95 % CI: 0.26–2.38, p = 0.8) coronary artery lesions after effective reperfusion in the comparison group. Associative relations between increased risk of heart failure have been established in single-vessel (OR = 4.67; 95 % CI: 0.29–90.01, p = 0.4) and multivessel (OR = 3.29; 95 % CI: 0.74–16.66, p = 0.01; χ2 = 5.71) coronary artery lesions after ineffective revascularization.
The role of anticoagulants in the treatment of community-acquired pneumonia in patients combined with coronavirus infection
Authors: Fushtei I. M. , Mochonyi V. O. , Soloviov O. V.
Published: February 2025

The review article focuses on the role of anticoagulants in the treatment of community-acquired pneumonia in patients combined with coronavirus infection. Considerable research interest in determining the role of anticoagulants, especially heparin, in COVID-19 patients is related to their positive effect on the disease course. Apart from well-known anticoagulant effects of unfractionated and low-molecular-weight heparins, they possess excellent pleiotropic properties. Although recommended, standard pharmacological thromboprophylaxis for hospitalized patients is debatable as there is still an issue regarding regimens and dosage in critically ill patients with pneumonia combined with COVID-19.
Aim. To define the role of anticoagulants in the treatment of community-acquired pneumonia in patients combined with coronavirus infection.
Materials and methods. Scientometric databases (PubMed, Web of Science and Scopus) were searched to retrospectively analyze literary sources focused on the specified issue selecting the most relevant ones for the period 2020–2024. Following evaluation of abstracts and full texts, 41 sources were retrieved.
Results. The pathogenesis of coagulopathy associated with COVID-19 is complex. It involves macrophage activation, the onset of “cytokine storm”, increased platelet adhesion and endothelial dysfunction, ultimately activating the intrinsic and extrinsic coagulation pathways. There is an increased risk of thromboembolism associated with COVID-19, and prophylactic anticoagulation improves outcomes in hospitalized patients. The problem for physicians is to decide which anticoagulant and how to start anticoagulation. Anticoagulant selection should take into consideration not only biochemical and coagulation parameters, such as elevated D-dimer, fibrinogen, and low antithrombin, which are the targets of this therapy. It is also extremely important to take into account bleeding risks, as massive bleeding can occur in 2.3 % of all patients, even when using standard doses for thromboprophylaxis. The use of anticoagulants such as heparin and vitamin K antagonists in COVID-19 patients is a challenging issue that depends on the balance between therapeutic benefit and potential risk avoidance. Therefore, thromboprophylaxis is indispensable for hospitalized patients with COVID-19.
Conclusions. Thus, the literature analysis has shown anticoagulant therapy as an integral component in the treatment of community-acquired pneumonia in patients combined with coronavirus infection for thromboprophylaxis. Heparin has been found to have a high therapeutic potential in patients with community-acquired pneumonia combined with coronavirus infection, but the bleeding risk should be weighed up. Enoxaparin is proved to be a safer anticoagulant option compared to heparin, but it may be not sufficiently effective in patients with community-acquired pneumonia combined with coronavirus infection.
Impairment of renal reserve filtration capacity in stage II–III chronic obstructive pulmonary disease under conditions of syntropy with stage II essential hypertension
Authors: Dotsenko S. Ya. , Akimova L. S.
Published: February 2025

The aim of the study: to examine the state of functional renal reserve in patients with stage II–III chronic obstructive pulmonary disease (COPD) and stage II essential hypertension (EH).
Materials and methods. 60 patients were examined and divided into 3 clinical groups: group 1 – 15 patients with stage II EH (mean age 52.87 ± 1.36 years; male / female ratio 73.33 % / 26.67 %); group 2 – 15 patients with stage III–III COPD (mean age 48.01 ± 2.75 years; male / female ratio 86.67 % / 13.33 %); group 3 – 30 patients with stage II–III COPD and comorbid stage II EH with arterial hypertension stage I–III (23 men and 7 women, mean age 57.49 ± 2.39 years), without evidence for another clinically significant concomitant pathology and who did not receive regular antihypertensive therapy. All the groups were comparable in sex distribution and demographic parameters. Data indicating the presence of clinically significant kidney disease in these individuals was not revealed by comprehensive clinical, laboratory and instrumental examination results.
Results. Functional renal reserve (FRR) in patients with COPD + EH was significantly lower by 3.79 times (p < 0.05) compared to that in otherwise healthy individuals, while the basal glomerular filtration rate (GFR) did not differ significantly between these groups. In EH monopathology, the FRR level was 2.11 times (p < 0.05) lower than that in the control group. In COPD comorbid with EH, almost 5/6 patients showed signs of renal dysfunction in the form of impaired renal reserve ability to proportionally increase GFR, indicating the progression of nephron hyperfiltration processes. According to the Pearson’s chi-squared test, adverse disorders of pulmonary respiratory function were significantly more common (decreased Tiffeneau index (χ2 = 6.13, p = 0.013)) as well as cases of microalbuminuria combined with elevated renal interlobar artery resistance (RI ILRA >1.05 RU) (χ2 = 13.64, p < 0.001) in COPD patients with EH in the lower quartile of the FRR index, indicating the possible parallelism in certain pathological processes and abnormal autoregulatory mechanisms of glomerular filtration in combination of COPD and EH.
Conclusions. In patients with comorbid stage II–III COPD and stage II EH, manifestations of intraglomerular hypertension and hyperfiltration progression are associated with more severe clinical symptoms and the degree of “pressure load” according to the results of 24-hour ambulatory blood pressure monitoring, as evidenced by the presence of statistically significant correlations between FRR values, on the one hand, and the COPD Assessment Test scores and daytime systolic blood pressure load index (r = +0.55 and -0.63, p < 0.05 for all cases), on the other, confirming important relationships between impaired intrarenal hemodynamic processes and some prognostic factors in COPD combined with EH.
The glucose-potassium ratio as a marker of adverse prognosis in patients with chronic heart failure
Authors: Syvolap V. V. , Lysenko V. A.
Published: February 2025

The glucose-potassium ratio (GPR) has previously proven its prognostic role in acute pathological conditions: ischemic and hemorrhagic strokes, aortic aneurysm and dissection, myocardial infarction. However, changes in the serum GPR in patients with chronic heart failure (CHF) with preserved left ventricular ejection fraction (HFpEF) remain unclear. It is known that tubulointerstitial injury occurs in patients with CHF. The renal tubulointerstitium plays a leading role in the reabsorption of glucose, potassium, and sodium. Therefore, impaired glucose-potassium ratio in patients with CHF is expected.
Aim. To examine changes in the glucose-potassium ratio in patients with ischemic HFpEF and to determine its impact on the short-term (1 year) prognosis.
Materials and methods. The study involved 57 patients (men – 43.9 % (n = 25); women – 56.1 % (n = 32)) with ischemic CHF, stage II A–B, NYHA FC II–IV, 49.1 % (n = 28) with sinus rhythm, and 50.9 % (n = 29) with atrial fibrillation (AF). Patients with sinus rhythm and AF were comparable in age (p = 0.968), height (p = 0.167), weight (p = 0.539), BMI (p = 0.774), body surface area (p = 0.296). The serum GPR was calculated as the serum glucose level divided by the serum potassium level. ROC analysis and logistic regression analysis were performed.
Results. According to the univariate regression model, an increase in the GPR above 1.1697 increased the number of adverse cardiovascular events by 11.15 times at the end of the 1st year of follow-up (95 % CI 1.33–93.50, p = 0.0048).
Conclusions. Chronic heart failure with preserved left ventricular ejection fraction is accompanied by impaired tubulointerstitial function, which is confirmed by an increase in the glucose-potassium ratio, and its increase above 1.1697 (sensitivity 88.9 %, specificity 60.8 %) is associated with 11.15 times (p = 0.0048) higher odds ratio of adverse cardiovascular events within a year.
Re-reading of Kim Hwan-Tae’s Criticism in the 1930s: an Aestheticist’s ‘Disinterested’ Wait
Authors: Park Hyunik
Published: February 2025

This article examines the significance of Kim Hwan-tae’s literary criticism in the 1930s, focusing on the core principles of aestheticism and its connection to Park Yong-chul’s poetry. Kim Hwan-tae’s criticism of impressionism has been interpreted as an advocacy for the value of pure literature, serving as a counterpoint to the dogmatic criticism championed by KAPF in the 1920s. Discussions of his criticism have often focused on the influence of figures such as Matthew Arnold and Walter Pater. This study argues that Kim Hwan-tae’s promotion of impressionism or art supremacy constituted a strategic framework aimed at transforming the roles of both authors and critics, extending beyond mere opposition to the Korean Artists Proletariat Federation (KAPF) position. His emphasis on ‘humility (겸허/謙虛)’ and ‘discipline (수양/修養)’ as essential qualities for critics reflects his ideal of aestheticism. Moreover, the critic’s model he advocated, which prioritizes self-discipline and holistic cultivation of personality, draws on Romanticism’s ‘genius theory (천재론)’ and German cultural discourse (독일 교양론), making it a distinctive feature of Kim Hwan-tae’s criticism.
Subjective well-being of women undergoing in vitro fertilization and embryo transfer and influencing factors
Authors: Zhang Xi , Li Jinlu , Wang Liye , Wang Zirui , Gou Xuemei , Song Donghong , Yang Rui
Published: February 2025

Objectives

Infertility is a global medical problem with annually increasing prevalence. In China, since the implementation of the universal two-child policy, the demand for fertility treatments continues to rise. During treatment, women with infertility may undergo various negative emotions, which can affect the treatment outcome, or even lead to refusal or discontinuation of treatment. However, maintaining a positive psychology can help alleviate negative emotions and increase patients’ confidence during the treatment process. The aim of this study is to investigate the subjective well-being (SWB) of infertile women undergoing the treatment of in vitro fertilization and embryo transfer (IVF-ET), and to analyze the factors affecting their psychological status during IVF-ET treatment.

Methods

In this study, 1,042 subjects were selected through convenience sampling from female subjects who received IVF-ET treatment from November 2021 to April 2022 at the Reproductive Medicine Center of a Grade A tertiary hospital in Beijing. All subjects were required to complete a basic profile questionnaire, self-esteem scale, fertility problem inventory (FPI), and SWB scale. A stepwise multiple linear regression was performed to analyze the factors impacting SWB.

Results

The mean score of SWB given by subjects was 88.97±12.08 (mean±standard deviation (SD)). The main factors influencing SWB included age, occupational status, personal monthly income, duration of infertility, self-esteem, and fertility stress (p<0.05), which together explain 51.5 % of total variance.

Conclusions

Overall, female subjects receiving IVF-ET treatment have a moderate level of SWB, which is affected by various factors. Our study suggests that clinical care should identify factors influencing SWB and provide interventions to enhance SWB of infertile women during IVF-ET treatment in order to encourage them to face treatment positively.