The choice of targeted therapies for treatment of glioblastoma patients is currently limited, and... more The choice of targeted therapies for treatment of glioblastoma patients is currently limited, and most glioblastoma patients die from the disease recurrence. Thus, systematic studies in simplified model systems are required to pinpoint the choice of targets for further exploration in clinical settings. Here, we report screening of 5 compounds targeting epigenetic writers or erasers and 6 compounds targeting cell cycle-regulating protein kinases against 3 glioblastoma cell lines following incubation under normoxic or hypoxic conditions. The viability assay indicated that PRMT5 inhibitor onametostat was endowed with high potency under both normoxic and hypoxic conditions in both MGMT-positive and MGMT-negative cell lines. In U-251 MG and U-87 MG cells, onametostat also affected the spheroid formation at concentrations lower than the currently used chemotherapeutic drug lomustine. Furthermore, in T98-G cell line, treatment with onametostat led to dramatic changes in the transcriptome p...
BACKGROUND Endometriosis is a debilitating and difficult-to-diagnose gynecological disease. Owing... more BACKGROUND Endometriosis is a debilitating and difficult-to-diagnose gynecological disease. Owing to limited information and awareness, women often rely on social media platforms as a support system to engage in discussions regarding their disease-related concerns. OBJECTIVE This study aimed to apply computational techniques to social media posts to identify discussion topics about endometriosis and to identify themes that require more attention from health care professionals and researchers. We also aimed to explore whether, amid the challenging nature of the disease, there are themes within the endometriosis community that gather posts with positive sentiments. METHODS We retrospectively extracted posts from the subreddits r/Endo and r/endometriosis from January 2011 to April 2022. We analyzed 45,693 Reddit posts using sentiment analysis and topic modeling–based methods in machine learning. RESULTS Since 2011, the number of posts and comments has increased steadily. The posts were categorized into 11 categories, and the highest number of posts were related to either asking for information (Question); sharing the experiences (Rant/Vent); or diagnosing and treating endometriosis, especially surgery (Surgery related). Sentiment analysis revealed that 92.09% (42,077/45,693) of posts were associated with negative sentiments, only 2.3% (1053/45,693) expressed positive feelings, and there were no categories with more positive than negative posts. Topic modeling revealed 27 major topics, and the most popular topics were Surgery, Questions/Advice, Diagnosis, and Pain. The Survey/Research topic, which brought together most research-related posts, was the last in terms of posts. CONCLUSIONS Our study shows that posts on social media platforms can provide insights into the concerns of women with endometriosis symptoms. The analysis of the posts confirmed that women with endometriosis have to face negative emotions and pain daily. The large number of posts related to asking questions shows that women do not receive sufficient information from physicians and need community support to cope with the disease. Health care professionals should pay more attention to the symptoms and diagnosis of endometriosis, discuss these topics with patients to reduce their dissatisfaction with doctors, and contribute more to the overall well-being of women with endometriosis. Researchers should also become more involved in social media and share new science-based knowledge regarding endometriosis.
IntroductionThe expression of genes in female reproductive organs is influenced by the cyclic cha... more IntroductionThe expression of genes in female reproductive organs is influenced by the cyclic changes in hormone levels during the menstrual cycle. While the molecular changes in the endometrium that facilitate embryo implantation have been extensively studied, there is limited knowledge about the impact of the menstrual cycle on cervical cells. Cervical cells can be easily and routinely collected using a cytobrush during gynecological examination, offering a standardized approach for diagnostic testing. In this study we investigated how the transcriptome of cervical cells changes during the menstrual cycle and assessed the utility of these cells to determine endometrial receptivity.MethodsEndocervical cells were collected with cytobrushes from 16 healthy women at different menstrual cycle phases in natural cycles and from four women undergoing hormonal replacement cycles. RNA sequencing was applied to gain insight into the transcriptome of cervical cells.ResultsTranscriptome analys...
Childhood medulloblastoma is a malignant form of brain tumor that is widely classified into four ... more Childhood medulloblastoma is a malignant form of brain tumor that is widely classified into four subgroups based on molecular and genetic characteristics. Accurate classification of these subgroups is crucial for appropriate treatment, monitoring plans, and targeted therapies. However, misclassification between groups 3 and 4 is common. To address this issue, an AI-based R package called MBMethPred was developed based on DNA methylation and gene expression profiles of 763 medulloblastoma samples to classify subgroups using machine learning and neural network models. The developed prediction models achieved a classification accuracy of over 96% for subgroup classification by using 399 CpGs as prediction biomarkers. We also assessed the prognostic relevance of prediction biomarkers using survival analysis. Furthermore, we identified subgroup-specific drivers of medulloblastoma using functional enrichment analysis, Shapley values, and gene network analysis. In particular, the genes inv...
Background Endometriosis is a debilitating and difficult-to-diagnose gynecological disease. Owing... more Background Endometriosis is a debilitating and difficult-to-diagnose gynecological disease. Owing to limited information and awareness, women often rely on social media platforms as a support system to engage in discussions regarding their disease-related concerns. Objective This study aimed to apply computational techniques to social media posts to identify discussion topics about endometriosis and to identify themes that require more attention from health care professionals and researchers. We also aimed to explore whether, amid the challenging nature of the disease, there are themes within the endometriosis community that gather posts with positive sentiments. Methods We retrospectively extracted posts from the subreddits r/Endo and r/endometriosis from January 2011 to April 2022. We analyzed 45,693 Reddit posts using sentiment analysis and topic modeling–based methods in machine learning. Results Since 2011, the number of posts and comments has increased steadily. The posts were...
Background Prenatal alcohol exposure (PAE) affects embryonic development, causing a variable feta... more Background Prenatal alcohol exposure (PAE) affects embryonic development, causing a variable fetal alcohol spectrum disorder (FASD) phenotype with neuronal disorders and birth defects. We hypothesize that early alcohol-induced epigenetic changes disrupt the accurate developmental programming of embryo and consequently cause the complex phenotype of developmental disorders. To explore the etiology of FASD, we collected unique biological samples of 80 severely alcohol-exposed and 100 control newborns at birth. Methods We performed genome-wide DNA methylation (DNAm) and gene expression analyses of placentas by using microarrays (EPIC, Illumina) and mRNA sequencing, respectively. To test the manifestation of observed PAE-associated DNAm changes in embryonic tissues as well as potential biomarkers for PAE, we examined if the changes can be detected also in white blood cells or buccal epithelial cells of the same newborns by EpiTYPER. To explore the early effects of alcohol on extraembryo...
Väitekirja elektrooniline versioon ei sisalda publikatsiooneDNA-s sisalduv geneetiline informatsi... more Väitekirja elektrooniline versioon ei sisalda publikatsiooneDNA-s sisalduv geneetiline informatsioon annab vajalikud juhised organismi kasvuks ja arenguks. Lisaks DNA nukleotiidsele järjestusele mõjutavad neid protsesse ka DNA-s esinevad modifikatsioonid. Enim uuritud DNA modifikatsioon on DNA metülatsioon, mis tähendab metüülrühma lisamist tsütosiini külge. DNA on tihtilugu metüleeritud regiooniti, moodustades niinimetatud metülatsioonimustreid. Need “mustrid“ osalevad geeniekspressiooni regulatsioonis, lülitades teatud rakkudes geene sisse ja välja või kohandades nende aktiivsust. On oluline märkida, et DNA metülatsioon on tugevalt mõjutatud keskkonnateguritest, nimelt vastavalt keskkonnatingimustele võidakse teatud regioone metüleerida või vastupidi, metüülrühmi eemaldada. Seega on DNA metülatsioon üheks vahelüliks geneetika ja keskkonna vahel. Paljud neist “mustritest“ on omased tavalistele bioloogilistele protsessidele, kuid leidub ka selliseid, mis viitavad haiguse olemasolule...
Cigarette smoking leads to serious epidemics in humans, creating torsion of infection in epitheli... more Cigarette smoking leads to serious epidemics in humans, creating torsion of infection in epithelial cells lining the respiratory tracts. Several researchers in the recent past have theorized that the next generation sequencing (NGS), especially transcriptome sequencing has enhanced understanding lung cancers and other epithelial epidemics. Conversely, pathogenesis specific to lung cancer with respect to molecular fraction of genomic ribonucleic acid has some mutant effect in various populations like smokers with lung cancer, healthy never smokers and vice versa. We review the impending impact of NGS data while providing insights into the biology of lung cancer affecting various populations, which we believe would be an add-on service for predictive biology approaches. Furthermore, we conclude what would be the outcome of such analysis for Indian population. Bioinformatics analysis was performed using various tools. We identified five genes namely epidermal growth factor receptor, Kirsten rat sarcoma, adenomatosis polyposis down regulated-1, N-ethylmaleimide-sensitive factor attachment protein, gamma and Piezo type mechanosensitive ion channel component 2 whose role was implicated in lung cancer and further analysis has to be performed to check whether or not the genes are indeed completely involved in causing lung cancer.
The choice of targeted therapies for treatment of glioblastoma patients is currently limited, and... more The choice of targeted therapies for treatment of glioblastoma patients is currently limited, and most glioblastoma patients die from the disease recurrence. Thus, systematic studies in simplified model systems are required to pinpoint the choice of targets for further exploration in clinical settings. Here, we report screening of 5 compounds targeting epigenetic writers or erasers and 6 compounds targeting cell cycle-regulating protein kinases against 3 glioblastoma cell lines following incubation under normoxic or hypoxic conditions. The viability assay indicated that PRMT5 inhibitor onametostat was endowed with high potency under both normoxic and hypoxic conditions in both MGMT-positive and MGMT-negative cell lines. In U-251 MG and U-87 MG cells, onametostat also affected the spheroid formation at concentrations lower than the currently used chemotherapeutic drug lomustine. Furthermore, in T98-G cell line, treatment with onametostat led to dramatic changes in the transcriptome p...
BACKGROUND Endometriosis is a debilitating and difficult-to-diagnose gynecological disease. Owing... more BACKGROUND Endometriosis is a debilitating and difficult-to-diagnose gynecological disease. Owing to limited information and awareness, women often rely on social media platforms as a support system to engage in discussions regarding their disease-related concerns. OBJECTIVE This study aimed to apply computational techniques to social media posts to identify discussion topics about endometriosis and to identify themes that require more attention from health care professionals and researchers. We also aimed to explore whether, amid the challenging nature of the disease, there are themes within the endometriosis community that gather posts with positive sentiments. METHODS We retrospectively extracted posts from the subreddits r/Endo and r/endometriosis from January 2011 to April 2022. We analyzed 45,693 Reddit posts using sentiment analysis and topic modeling–based methods in machine learning. RESULTS Since 2011, the number of posts and comments has increased steadily. The posts were categorized into 11 categories, and the highest number of posts were related to either asking for information (Question); sharing the experiences (Rant/Vent); or diagnosing and treating endometriosis, especially surgery (Surgery related). Sentiment analysis revealed that 92.09% (42,077/45,693) of posts were associated with negative sentiments, only 2.3% (1053/45,693) expressed positive feelings, and there were no categories with more positive than negative posts. Topic modeling revealed 27 major topics, and the most popular topics were Surgery, Questions/Advice, Diagnosis, and Pain. The Survey/Research topic, which brought together most research-related posts, was the last in terms of posts. CONCLUSIONS Our study shows that posts on social media platforms can provide insights into the concerns of women with endometriosis symptoms. The analysis of the posts confirmed that women with endometriosis have to face negative emotions and pain daily. The large number of posts related to asking questions shows that women do not receive sufficient information from physicians and need community support to cope with the disease. Health care professionals should pay more attention to the symptoms and diagnosis of endometriosis, discuss these topics with patients to reduce their dissatisfaction with doctors, and contribute more to the overall well-being of women with endometriosis. Researchers should also become more involved in social media and share new science-based knowledge regarding endometriosis.
IntroductionThe expression of genes in female reproductive organs is influenced by the cyclic cha... more IntroductionThe expression of genes in female reproductive organs is influenced by the cyclic changes in hormone levels during the menstrual cycle. While the molecular changes in the endometrium that facilitate embryo implantation have been extensively studied, there is limited knowledge about the impact of the menstrual cycle on cervical cells. Cervical cells can be easily and routinely collected using a cytobrush during gynecological examination, offering a standardized approach for diagnostic testing. In this study we investigated how the transcriptome of cervical cells changes during the menstrual cycle and assessed the utility of these cells to determine endometrial receptivity.MethodsEndocervical cells were collected with cytobrushes from 16 healthy women at different menstrual cycle phases in natural cycles and from four women undergoing hormonal replacement cycles. RNA sequencing was applied to gain insight into the transcriptome of cervical cells.ResultsTranscriptome analys...
Childhood medulloblastoma is a malignant form of brain tumor that is widely classified into four ... more Childhood medulloblastoma is a malignant form of brain tumor that is widely classified into four subgroups based on molecular and genetic characteristics. Accurate classification of these subgroups is crucial for appropriate treatment, monitoring plans, and targeted therapies. However, misclassification between groups 3 and 4 is common. To address this issue, an AI-based R package called MBMethPred was developed based on DNA methylation and gene expression profiles of 763 medulloblastoma samples to classify subgroups using machine learning and neural network models. The developed prediction models achieved a classification accuracy of over 96% for subgroup classification by using 399 CpGs as prediction biomarkers. We also assessed the prognostic relevance of prediction biomarkers using survival analysis. Furthermore, we identified subgroup-specific drivers of medulloblastoma using functional enrichment analysis, Shapley values, and gene network analysis. In particular, the genes inv...
Background Endometriosis is a debilitating and difficult-to-diagnose gynecological disease. Owing... more Background Endometriosis is a debilitating and difficult-to-diagnose gynecological disease. Owing to limited information and awareness, women often rely on social media platforms as a support system to engage in discussions regarding their disease-related concerns. Objective This study aimed to apply computational techniques to social media posts to identify discussion topics about endometriosis and to identify themes that require more attention from health care professionals and researchers. We also aimed to explore whether, amid the challenging nature of the disease, there are themes within the endometriosis community that gather posts with positive sentiments. Methods We retrospectively extracted posts from the subreddits r/Endo and r/endometriosis from January 2011 to April 2022. We analyzed 45,693 Reddit posts using sentiment analysis and topic modeling–based methods in machine learning. Results Since 2011, the number of posts and comments has increased steadily. The posts were...
Background Prenatal alcohol exposure (PAE) affects embryonic development, causing a variable feta... more Background Prenatal alcohol exposure (PAE) affects embryonic development, causing a variable fetal alcohol spectrum disorder (FASD) phenotype with neuronal disorders and birth defects. We hypothesize that early alcohol-induced epigenetic changes disrupt the accurate developmental programming of embryo and consequently cause the complex phenotype of developmental disorders. To explore the etiology of FASD, we collected unique biological samples of 80 severely alcohol-exposed and 100 control newborns at birth. Methods We performed genome-wide DNA methylation (DNAm) and gene expression analyses of placentas by using microarrays (EPIC, Illumina) and mRNA sequencing, respectively. To test the manifestation of observed PAE-associated DNAm changes in embryonic tissues as well as potential biomarkers for PAE, we examined if the changes can be detected also in white blood cells or buccal epithelial cells of the same newborns by EpiTYPER. To explore the early effects of alcohol on extraembryo...
Väitekirja elektrooniline versioon ei sisalda publikatsiooneDNA-s sisalduv geneetiline informatsi... more Väitekirja elektrooniline versioon ei sisalda publikatsiooneDNA-s sisalduv geneetiline informatsioon annab vajalikud juhised organismi kasvuks ja arenguks. Lisaks DNA nukleotiidsele järjestusele mõjutavad neid protsesse ka DNA-s esinevad modifikatsioonid. Enim uuritud DNA modifikatsioon on DNA metülatsioon, mis tähendab metüülrühma lisamist tsütosiini külge. DNA on tihtilugu metüleeritud regiooniti, moodustades niinimetatud metülatsioonimustreid. Need “mustrid“ osalevad geeniekspressiooni regulatsioonis, lülitades teatud rakkudes geene sisse ja välja või kohandades nende aktiivsust. On oluline märkida, et DNA metülatsioon on tugevalt mõjutatud keskkonnateguritest, nimelt vastavalt keskkonnatingimustele võidakse teatud regioone metüleerida või vastupidi, metüülrühmi eemaldada. Seega on DNA metülatsioon üheks vahelüliks geneetika ja keskkonna vahel. Paljud neist “mustritest“ on omased tavalistele bioloogilistele protsessidele, kuid leidub ka selliseid, mis viitavad haiguse olemasolule...
Cigarette smoking leads to serious epidemics in humans, creating torsion of infection in epitheli... more Cigarette smoking leads to serious epidemics in humans, creating torsion of infection in epithelial cells lining the respiratory tracts. Several researchers in the recent past have theorized that the next generation sequencing (NGS), especially transcriptome sequencing has enhanced understanding lung cancers and other epithelial epidemics. Conversely, pathogenesis specific to lung cancer with respect to molecular fraction of genomic ribonucleic acid has some mutant effect in various populations like smokers with lung cancer, healthy never smokers and vice versa. We review the impending impact of NGS data while providing insights into the biology of lung cancer affecting various populations, which we believe would be an add-on service for predictive biology approaches. Furthermore, we conclude what would be the outcome of such analysis for Indian population. Bioinformatics analysis was performed using various tools. We identified five genes namely epidermal growth factor receptor, Kirsten rat sarcoma, adenomatosis polyposis down regulated-1, N-ethylmaleimide-sensitive factor attachment protein, gamma and Piezo type mechanosensitive ion channel component 2 whose role was implicated in lung cancer and further analysis has to be performed to check whether or not the genes are indeed completely involved in causing lung cancer.
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