imagine (Institute of molecular genetics and genetic engineering)
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Supervised Machine Learning Approach for Prediction of Occult Lymph Node Metastasis in T1-T2 Papillary Thyroid Carcinoma
Get PDFThis study aimed to assess and compare four machine learning (ML) based classifiers in
predicting occult cervical lymph node metastasis (LNM) in clinically node-negative (cN0),
T1-T2 papillary thyroid carcinoma (PTC) patients.
The study cohort included 288 PTC patients who underwent total thyroidectomy and
prophylactic central neck dissection with sentinel lymph node biopsy performed for
lateral LNM identification. The classifiers, namely k-Nearest Neighbor (k-NN), Support
Vector Machines, Decision Tree, and Logistic Regression were developed using patients’
demographic and clinicopathological variables. Evaluation metrics such as area under the
receiver operating characteristic curve (AUC), sensitivity, specificity, positive and negative
predictive values (PPV and NPV), accuracy, and F1 and F2 scores were utilized for model
comparison.
The final ML classifier was selected based on achieving the highest specificity and the
lowest degree of overfitting while maintaining a sensitivity of 95%. Among the evaluated
models, the k-NN emerged as the best-performing, demonstrating an AUC of 0.72. The
sensitivity, specificity, PPV, NPV, F1, and F2 scores were 98%, 27%, 56%, 93%, 72%, and
85%, respectively Furthermore, a web application was developed allowing users to predict
the potential of cervical LNM and explore possibilities for further model development.
The k-NN classifier incorporating patients’ clinicopathological information shows potential
in predicting LNM. Improved prediction models are necessary to identify patients at higher
risk of LNM, guiding appropriate postsurgical treatment for high-risk individuals while
minimizing unnecessary interventions for low-risk patients.Book of abstract: 4th Belgrade Bioinformatics Conference, June 19-23, 202
Exploring Changes in Diagnoses during the COVID-19 Era: Comparative Analysis
Get PDFThe healthcare sector is just one of several areas of society that have been significantly impacted
by the COVID-19 pandemic. This paper aims to analyze the changes observed in the medical
profession’s approach to diagnosing diseases between the pre-pandemic year of 2019 and the
pandemic year of 2020. By examining these shifts, we explore how medical professionals have
adapted their treatment strategies, leading to modifications in diagnosis for various diseases.
Based on our visualization, shown in Figure 1, we observed that the diagnoses of Obstructive
Sleep Apnea and End stage renal disease had consistent distributions in both 2019 and 2020.
Also we need to mention, the count value for Obstructive Sleep Apnea was higher in 2020,
whereas in 2019, the count value was higher for End stage renal disease, showing their
representation in each year. We can conclude that the pandemic has resulted in a marked
increase in the occurrence of specific diagnoses compared to the previous year, some of them
being acute pharyngitis-sore throat (J029), gastro-oesophageal reflux disease (K219) and pure
hypercholesterolemia - unspecified (E7800), as can be seen on Figure 1.
A notable variation can be observed when examining the months of November and December
in 2020. In these months, the diagnosis Contact with and (suspected) exposure to other viral
communicable diseases transitions from the third to the second position, indicating a higher
occurrence of COVID-19 in December compared to November. This shift in ranking provides
valuable insights into the increased prevalence of this diagnosis during the month of December.
Through this analysis, we aim to examine the transformations that have taken place as
a result of the pandemic, particularly in terms of the diagnosis of a specific disease, which
has undergone notable changes compared to the pre-pandemic period. We highlight several
significant changes that have occurred in defining diagnoses, showcasing the variations
observed over the course of a year.Book of abstract: 4th Belgrade Bioinformatics Conference, June 19-23, 202
Brackish Groundwaters Contain Plastic- and Cellulose-Degrading Bacteria
No full textThe selected brackish groundwater occurrences in the geotectonic regions of Inner Dinarides of western Serbia (Obrenovačka Banja) and Serbian crystalline core (Lomnički Kiseljak and Velika Vrbnica) were sampled for isolation and identification of plastic- and lignocellulose-degrading bacteria, as well as for the assessment of their enzymatic potential. The examined occurrences belong to the cold and warm (subthermal), weakly alkaline, neutral, and weakly acidic groundwater, and their genetic types are HCO3–Na + K and HCO3–Ca, Mg. The most abundant genera identified by next-generation 16S sequencing of cultivated groundwater samples belong to Aeromonas and Exiguobacterium. Of isolates screened on plastic and lignocellulosic substrates, 85.3% demonstrated growth and/or degrading activity on at least one tested substrate, with 27.8% isolates degrading plastic substrate Impranil® DLN-SD (SD), 1.9% plastic substrate bis(2-hydroxyethyl)terephthalate, and 5.6% carboxymethyl cellulose (CMC). Isolates degrading SD that were identified by 16S rDNA sequencing belonged to genera Stenotrophomonas, Flavobacterium, Pantoea, Enterobacter, Pseudomonas, Serratia, Acinetobacter, and Proteus, while isolates degrading CMC belonged to genera Rhizobium and Shewanella. All investigated brackish groundwaters harbor bacteria with potential in degradation of plastics or cellulose. Taking into account that microplastics contamination of groundwater resources is becoming a significant problem, the finding of plastic-degrading bacteria may have potential in bioremediation treatments of polluted groundwater. Subterranean ecosystems, which are largely untapped resources of biotechnologically relevant enzymes, are not traditionally considered the environment of choice for screening for plastic- and cellulose-degrading bacteria and therefore deserve a special attention from this aspect.SharedIt link:[https://link.springer.com/epdf/10.1007/s00248-023-02278-8?sharing_token=gGjTVHQocoXNYgn3NbBnHPe4RwlQNchNByi7wbcMAY7TWS5C4xsEjZ19Ncu1lyDt74UKPsL6r9TSBPuFqRUTbm0t3FZeOcOBDVdIk79dwTQCgCFvLJlCMf2aUrrJJKHlCtl4XBAfMxPgnxJrYBpScFJaoFdfYERSg7Zc57lkuPs%3D]Sequence data The 16S rDNA sequence datasets for cultivated groundwater samples are deposited in the NCBI BioProject database [https:// datav iew. ncbi. nlm. nih. gov/ object/ PRJNA 951531? revie wer= 31vmq vhf0g i8su4 ispc5 qkspvg
Pharmacogenetic markers of response to therapy with thiopurine drugs, methotrexate, and vincristine in children with acute lymphoblastic leukemia
No full textAkutna limfoblastna leukemija (ALL) je najčešći malignitet dečjeg doba. Napredak ulečenju usmeren je ka smanjenju pojave neželjenih efekata terapije, primenom principafarmakogenetike.U ovoj studiji istraživanje je bilo usmereno ka otkrivanju farmakogenetičkih ifarmakotranskriptomskih markera odgovora na lekove koji su okosnica terapijskih protokola lečenjadece obolele od ALL (tiopurinski lekovi, metotreksat i vinkristin).Analizirani su uzorci krvi i koštane srži 139 dece sa ALL. Varijante u ispitivanim genimadetektovane su metodom PCR-a i Sangerovim sekvenciranjem. Nivo ekspresije NUDT15 umononuklearnim ćelijama određen je real-time PCR-om. Korelacija farmakomarkera sa kliničkimparametrima vršena je statističkim testovima.Odgovor na ispitivane lekove procenjivan je u retrospektivnim kliničkim studijama.Pokazano je da nivo ekspresije NUDT15 na prezentaciji bolesti ne korelira sa pojavom neželjenihefekata terapije tiopurinskim lekovima. U ispitivanoj grupi detektovano je 5 varijanti u genuNUDT15 koje nemaju patogeni efekat. Varijanta rs4149056 u genu SLCO1B1 je izučavana kaomarker farmakokinetike i toksičnosti metotreksata. U ovoj studiji nije potvrđen njen klinički značaj.Analiziran je farmakogenetički potencijal varijanti u genima CYP3A5, CEP72, ACTG1, MIR3117 iMIR4481 kao markera odgovora na terapiju vinkristinom. Nije potvrđena korelacija ovih varijantisa nastankom perifernih neuropatija kod dece sa ALL. Razvijen je predikcioni model zahepatotoksičnost izazvanu metotreksatom, zasnovan na poligenskom skoru rizika.Ova studija je doprinela znanjima koja vode ka personalizaciji lečenja dece obolele od ALL.Acute lymphoblastic leukemia (ALL) is the most common childhood malignancy.Treatment progress is aimed at reducing the occurrence of side effects of therapy, by applying theprinciples of pharmacogenetics.The aim of this study was to discover pharmacogenetic and pharmacotranscriptomicmarkers of response to drugs that are the backbone of therapeutic protocols for the treatment ofchildren with ALL (thiopurine drugs, methotrexate and vincristine).Blood and bone marrow samples of 139 children with ALL were analysed. Variants in thetested genes were detected by PCR and Sanger sequencing. The expression level of NUDT15 inmononuclear cells was determined by real-time PCR. The correlation of pharmacomarkers withclinical parameters was performed using statistical tests.The response to the investigated drugs was evaluated in retrospective clinical studies. It wasshown that the level of NUDT15 expression at the presentation of the disease does not correlatewith the occurrence of side effects of thiopurine drug therapy. In this study 5 variants in theNUDT15 gene were detected, which do not have a pathogenic effect. The rs4149056 variant in theSLCO1B1 gene was assessed as a marker of methotrexate pharmacokinetics and toxicity. Its clinicalsignificance was not confirmed in this study. The pharmacogenetic potential of variants in CYP3A5,CEP72, ACTG1, MIR3117 and MIR4481 genes as markers of response to vincristine therapy wasanalysed. The correlation of these variants with the onset of peripheral neuropathies in children withALL has not been confirmed. A predictive model for methotrexate-induced hepatotoxicity based onthe polygenic risk score was developed.This study contributed to the knowledge that leads to the personalization of the treatment ofchildren with ALL
Molecular Biomarkers in Perthes Disease: A Review
Get PDFBackground: Perthes disease is a juvenile form of osteonecrosis of the femoral head that affects children under the age of 15. One hundred years after its discovery, some light has been shed on its etiology and the biological factors relevant to its etiology and disease severity. Methods: The aim of this study was to summarize the literature findings on the biological factors relevant to the pathogenesis of Perthes disease, their diagnostic and clinical significance, and their therapeutic potential. A special focus on candidate genes as susceptibility factors and factors relevant to clinical severity was made, where studies reporting clinical or preclinical results were considered as the inclusion criteria. PubMed databases were searched by two independent researchers. Sixty-eight articles were included in this review. Results on the factors relevant to vascular involvement and inflammatory molecules indicated as factors that contribute to impaired bone remodeling have been summarized. Moreover, several candidate genes relevant to an active phase of the disease have been suggested as possible biological therapeutic targets. Conclusions: Delineation of molecular biomarkers that underlie the pathophysiological process of Perthes disease can allow for the provision of earlier and more accurate diagnoses of the disease and more precise follow-ups and treatment in the early phases of the disease.Supplementary information:[https://hdl.handle.net/21.15107/rcub_imagine_2089
Detection of preleukemic clones in neonatal blood spots of children with B-cell precursor acute lymphoblastic leukemia
Get PDFIntroduction: Childhood B-cell precursor acute lymphoblastic leukemic (BCP-ALL) can be traced back to
birth using leukemic clone-specific immunoglobulin heavy chain (IGH) rearrangements, implying prenatal origin of this disease. The aim of this study was to analyze neonatal blood spots (Guthrie cards) of
childhood BCP-ALL patients for the presence of clonotypic IGH rearrangements.
Methods: The study enrolled 24 patients aged 1 to 9.6 years. Based on the sequences of IGH rearrangements identified in diagnostic lymphoblasts, 2 patient-specific primers were designed for each patient
and used in semi-nested PCR for the detection of preleukemic clones at birth.
Results: Clonotypic IGH rearrangements were detected in neonatal blood spots of 54.2% of patients. In
two cases that had double IGH rearrangements at diagnosis, only one rearrangement was present at
birth, while in the third case both leukemic rearrangements were detected in neonatal blood. Guthrie
card-positive findings were significantly more frequent in children ≤5 years of age than in older children
(p=0.011). Regarding patients’characteristics at birth and at diagnosis, Guthrie card-positivity was not associated with sex, birth weight and mother’s age, as well as with white blood cell count, percentage of
bone marrow blasts, immunophenotype and the presence of ETV6/RUNX1 and TCF3/PBX1 fusion genes
at diagnosis.
Conclusion: Our study confirms that a large proportion of childhood BCP-ALL originates in utero, regardless of the molecularsubtype defined by chromosomal aberrations. The latency period to the overt
leukemia depends on the presence of preleukemic clone at birth, as well as on the postnatal transforming genetic events
Microbes and microbial enzymes for degradation of (bio)plastics
Get PDFIntroduction: Plastic films, containers, and fibers are almost ubiquitous, making our life better, easier, and
safer. However, the uncontrollable disposal of plastic waste has raised global concern. Plastic pollution
is not a recent issue; it originated decades ago with the advent of industrial plastic production. While recycling, incineration, and other methods exist for managing plastic waste, unfortunately, landfilling remains the most prevalent“solution” adopted by many countries.
In response to the pressing issue of plastic pollution, a new scientific field has emerged, dedicated to
employing innovative green methodologies inspired by nature’s mechanisms. This approach centers
around the discovery and identification of microorganisms with the ability to harness the carbon derived from plastic waste for their growth and survival. In the context of this research, we aim to accomplish two main objectives: isolating enzymes expressed by diverse microbial strains and exploring the
potential of well-known hydrolytic enzymes in breaking down synthetic and biosourced polymers.
Methods: To optimize and improve biodegradation yields, our approach combines enzymatic and microbial plastic degradation with polymer treatment techniques. These techniques are designed to modify the structure of polymers, making them more accessible for hydrolysis and assimilation by
microorganisms. After polymer hydrolysis, our concept emphasizesthe recovery and utilization of the released compounds, which can be further converted into valuable bio-products through fermentation.
Results: Number of new enzymes, microorganisms and microbial communities has been isolated and
characterized with the potential to degrade both single and mixed plastic substrates.
Conclusion: By adopting this multidisciplinary approach, we aim to establish a sustainable pathway for
the efficient management of plastic waste. Through the transformation of polymers into high-added
value products such as bioplastics, biopigments and biosurfactants, we contribute to a circular economy plan and mitigate the environmental impact associated with plastic waste
Bacterial nanocellulose – new beginning for end-of-life plastics
Get PDFIntroduction: Fossil-based polymers continue to be widely used despite their negative environmental
impact. Bioplastics, such as polylactic acid (PLA), offer a promising alternative as they are derived from
renewable resources and provide more environmentally friendly end-of-life options. However, marketing PLA assimply biodegradable can be misleading, asthe current PLA degradation strategy contributes
to microplastics pollution, thus posing even greater threat. Thisresearch focuses on the upcycling of PLA
degradation products into valuable biomaterial - bacterial nanocellulose.
Methods: PLA samples were pretreated using ultraviolet and ultrasonic waves, individually and in combination, to enhancessusceptibility to bacterial degradation. Pretreated PLA wassubjected to enzymatic
degradation under mild conditions, using various enzyme combinations. The resulting biodegradation
products served as a growth medium for nanocellulose producing bacteria Komagataeibacter medellinensis ID13488. Obtained nanocellulose was characterized using SEM, FTIR, AFM, and XRD.
Results: The combined PLA pretreatment using ultraviolet and ultrasonic waves, followed by enzymatic
degradation with savinase, demonstrated the highest degree of PLA degradation in this study. Furthermore, K. medellinensis ID13488 efficiently utilized the biodegradation products, producing nanocellulose with yields and performance comparable to those obtained through standard cultivation using
glucose as a carbon source.
Conclusion: This study highlights the potential of combined pretreatment and enzymatic degradation
for efficient PLA degradation and sustainable bacterial nanocellulose production. The findings suggest
promising avenues for utilizing PLA biodegradation products in the production of other valuable biomaterials. Further research is needed to optimize the pretreatment and degradation processes, facilitating the wider application of biodegradable materials and promoting sustainability
Drought-induced Changes in the Antioxidant System in Pisum sativum L.
Get PDFBackground: This study was carried out for an understanding of the antioxidant mechanisms of field pea varieties under osmotic stress conditions caused by a lack of water. The activities of antioxidant enzymes such as superoxide dismutase (SOD), catalase (CAT), ascorbate peroxidase (APx) and glutathione reductase (GR) were examined and analyzed. The gene expression levels of Cu/Zn SOD, cAPx and GR genes were also examined. Methods: Osmotic stress was stimulated using PEG 6000 with the osmotic potential of -0.1 MPa in 10 days old plant seedlings. The activity of the antioxidant enzymes was measured in the shoots and roots of pea seedlings. The gene expression levels of genes coding antioxidative enzymes were examined by the reverse transcription polymerase chain reaction (RT-PCR) technique. Arabidopsis 18S rRNA was used as endogenous control. Result: Osmotic stress changed the activities of antioxidant enzymes in the shoots and roots of pea seedlings. Varieties more tolerant to osmotic stress showed a significant increase in antioxidant activities in shoots and roots, while sensitive varieties showed a significant decrease. The results of the analysis of the expression of genes, coding for antioxidant enzymes, showed that the reaction of the tested cultivars to ROS was the result of increased expression of the tested genes in tolerant cultivars, i.e. decreased expression in sensitive cultivars
Drought-induced Changes in the Antioxidant System in Pisum sativum L.
Get PDFBackground: This study was carried out for an understanding of the antioxidant mechanisms of field pea varieties under osmotic
stress conditions caused by a lack of water. The activities of antioxidant enzymes such as superoxide dismutase (SOD), catalase
(CAT), ascorbate peroxidase (APx) and glutathione reductase (GR) were examined and analyzed. The gene expression levels of
Cu/Zn SOD, cAPx and GR genes were also examined.
Methods: Osmotic stress was stimulated using PEG 6000 with the osmotic potential of -0.1 MPa in 10 days old plant seedlings. The
activity of the antioxidant enzymes was measured in the shoots and roots of pea seedlings. The gene expression levels of genes
coding antioxidative enzymes were examined by the reverse transcription polymerase chain reaction (RT-PCR) technique. Arabidopsis
18S rRNA was used as endogenous control.
Result: Osmotic stress changed the activities of antioxidant enzymes in the shoots and roots of pea seedlings. Varieties more
tolerant to osmotic stress showed a significant increase in antioxidant activities in shoots and roots, while sensitive varieties showed
a significant decrease. The results of the analysis of the expression of genes, coding for antioxidant enzymes, showed that the
reaction of the tested cultivars to ROS was the result of increased expression of the tested genes in tolerant cultivars, i.e. decreased
expression in sensitive cultivars