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Rarely, immunophenotypically immature B-cell precursor acute lymphoblastic leukemia (BCP-ALL) carries an immunoglobulin- MYC rearrangement (IG-MYC-r). This can result in diagnostic confusion with Burkitt lymphoma/leukemia and use of individualized treatment schedules of unproven efficacy. Here we compare the molecular characteristics of these conditions and investigate historic clinical outcome data. We identified 90 cases registered in a national BCP-ALL clinical trial/registry. When present, diagnostic material underwent cytogenetic, exome, methylome and transcriptome analyses. The outcomes analyzed were 3-year event-free survival and overall survival. IG-MYC-r was identified in diverse cytogenetic backgrounds, co-existing with either established BCP-ALL-specific abnormalities (high hyperdiploidy, n=3; KMT2A-rearrangement, n=6; iAMP21, n=1; BCR-ABL1, n=1); BCL2/BCL6-rearrangements (n=15); or, most commonly, as the only defining feature (n=64). Within this final group, precursor-like V(D)J breakpoints predominated (8/9) and KRAS mutations were common (5/11). DNA methylation identified a cluster of V(D)J-rearranged cases, clearly distinct from Burkitt leukemia/lymphoma. Children with IG-MYC-r within that subgroup had a 3-year event-free survival of 47% and overall survival of 60%, representing a high-risk BCP-ALL. To develop effective management strategies this group of patients must be allowed access to contemporary, minimal residual disease-adapted, prospective clinical trial protocols.

Due to the adverse environmental impacts of synthetic plastics, biodegradable plastics development for both industrial and commercial applications is essential for the present scenario. In addition to the non-degradability of petroleum-based plastic and its impacts, so it is very important to find an alternative to petroleum-based plastic. Starch-based bioplastics are an excessive substitute for petroleum-based plastics due to their significant properties compared with natural sources. This research aims to formalize five new formulas of bioplastic by combining two sources of starch, extracted from various biomass sources, its properties and comparison between them. The moisture content shows 2.07% and 0.984% for samples F and B respectively and that indicates that the samples which contain a high amount of corn starch have less moisture content. The highest results of biodegradation percentages were 68.27% and 52.6% which are for samples A and D respectively, and the lowest biodegradation percentage were 34.33% and 31.29% which are for samples F and B respectively.

Coronary Artery Disease (CAD) is the most common type of heart disease and a major cause of mortality worldwide. This study highlights the significance of hypertension as a risk factor in patients with CAD and compares its prevalence to those of EUROASPIRE IV (EUS-IV), ESC Atlas of Cardiology (Atlas) and Cyprus Survey of Coronary Heart Disease of 2006 (CY-2006). A retrospective, observational study was conducted, by the Registry of Cyprus Heart Survey, where 375 individuals with chronic CAD were examined in Nicosia General Hospital Cardiology Clinics, between the years 2011 and 2014. Their medical history regarding hypertension was noted and the data was analyzed using Microsoft Excel software. The total prevalence of hypertension, based on the past medical history of the patients was 59%. Out of these, 52% were found to have elevated blood pressure on their visit to the Cardiology Clinic. The total mean systolic blood pressure amongst the study group was 136 mmHg, with no significant differences between males and females (136 mmHg and 134 mmHg respectively). The findings of the present study are the same compared to those of the CY-2006 (52% both), but slightly higher than the findings of EUS-IV (52% vs. 42.7%) and significantly higher than those recorded in the Atlas (52% vs. 24.8%). The results show that there is still much potential to improve hypertension management in patients with established CAD.

Introduction Several studies have shown that the insomnia with objective short sleep duration (ISSD) phenotype is associated with stage 2 hypertension and type 2 diabetes. We aimed to determine if there is an association between ISSD and metabolic syndrome (MetS). Methods We studied 1,741 adults from the Penn State Adult Cohort (age 20-88 years, 52.3% female, 12.4% racial/ethnic minority) who underwent a 1-night polysomnographic (PSG) evaluation, clinical history, and physical examination. Insomnia was defined as a complaint of insomnia with a duration ≥ 1 year, while poor sleep was defined as a complaint of difficulty falling asleep, staying asleep, nonrestorative sleep or early morning awakening. Objective short sleep duration was defined as < 6-hours. MetS was defined by the presence of 3 or more of: BMI≥30 kg/m2, elevated total cholesterol (≥200 mg/dL), triglycerides (≥150 mg/dL), fasting glucose (≥100 mg/dL), or treatment, and blood pressure (≥130/85 mm Hg) or treatment. Logistic regression models examined the odds of developing MetS, while simultaneously adjusting for sex, race, age, alcohol, smoking, sleep-disordered breathing, mental and physical problems, and sampling weight. Results Compared to normal sleepers with normal sleep duration, ISSD was associated with a significantly increased risk of MetS (OR=2.04, 95%CI=1.13-3.70), while insomnia with normal sleep duration (INSD) was not (OR=1.03, 95%CI=0.53-1.99). Neither normal sleepers with short sleep duration nor poor sleeper with normal or short sleep duration were associated with increased risk of MetS. Further analysis of the clustering of the cardiometabolic risk factors revealed that in the ISSD group who had MetS, 94% had elevated blood pressure, 78% had elevated cholesterol, 72% had insulin resistance, 53% had elevated triglycerides, and 53% had BMI≥30 kg/m2. Conclusion These data indicate that hypercholesterolemia, but not hypertriglyceridemia or obesity, contributes to the association of ISSD with MetS. These data suggest that in addition to the previously-identified elevated blood pressure and insulin resistance, treatment of hypercholesterolemia in patients with ISSD may prevent the development of cardiovascular and cerebrovascular disease. Support (if any)

Chromosomal translocations are important drivers of haematological malignancies whereby proto-oncogenes are activated by juxtaposition with enhancers, often called enhancer hijacking. We analysed the epigenomic consequences of rearrangements between the super-enhancers of the immunoglobulin heavy locus (IGH) and proto-oncogene CCND1 that are common in B-cell malignancies. By integrating BLUEPRINT epigenomic data with DNA breakpoint detection, we characterised the normal chromatin landscape of the human IGH locus and its dynamics after pathological genomic rearrangement. We detected an H3K4me3 broad domain (BD) within the IGH locus of healthy B cells that was absent in samples with IGH-CCND1 translocations. The appearance of H3K4me3-BD over CCND1 in the latter was associated with overexpression and extensive chromatin accessibility of its gene body. We observed similar cancer-specific H3K4me3-BDs associated with hijacking of super-enhancers of other common oncogenes in B-cell (MAF, MYC and FGFR3/NSD2) and T-cell malignancies (LMO2, TLX3 and TAL1). Our analysis suggests that H3K4me3-BDs can be created by super-enhancers and supports the new concept of epigenomic translocation, where the relocation of H3K4me3-BDs from cell identity genes to oncogenes accompanies the translocation of super-enhancers.

Introduction Insomnia with objective short sleep duration (ISSD) has been associated with adverse cardiometabolic outcomes, including hypertension and diabetes. However, data on the association between ISSD and the development of cardiovascular and/or cerebrovascular disease (CBVD) are limited. We aimed to examine whether ISSD is associated with incident CBVD. Methods 1,211 men and women from the Penn State Adult Cohort (56.9% women, 51.82±12.85 years) without CBVD at baseline were followed up for 9.21±4.08 years. Based upon clinical history and physical examination, we defined the presence of CBVD as a history of diagnosis or treatment of heart disease and/or stroke. Insomnia was defined as a complaint of insomnia with a duration ≥ 1 year. Poor sleep was defined as a complaint of difficulty falling asleep, staying asleep, nonrestorative sleep or early morning awakening. Objective short sleep duration was defined as < 6-hours sleep based on a 1-night, 8-hours, in-lab polysomnography. Logistic regression models examined the odds of incident CBVD, while simultaneously adjusting for race, sex, age, BMI, smoking, alcohol use, physical and mental health problems, sleep-disordered breathing and follow-up duration. Results Compared to normal sleepers with normal sleep duration, the highest risk of incident CBVD was in the ISSD group (OR=2.68, 95%CI=1.17-6.14), and the second highest in normal sleepers with short sleep duration (OR=1.65, 95%CI=1.10-2.49). The risk for incident CBVD was not significantly increased, in poor sleepers or those with insomnia with normal sleep duration (INSD). Conclusion Our findings indicate that the combination of short sleep duration with the complaint of chronic insomnia (ISSD) is associated with an additive effect on incident heart disease and stroke. These data add to the cumulative evidence supporting the existence of two insomnia phenotypes and that ISSD is the more severe biological phenotype of the disorder associated with physiologic hyperarousal and cardiovascular morbidity. The diagnostic and treatment implications of insomnia phenotyping based on objective sleep duration will be discussed. Support (if any)

Introduction Insomnia with objective short sleep duration (ISSD) has been proposed as the most biologically severe phenotype of the disorder associated with cardiometabolic morbidity in population-based samples. Methods In this study, we investigated the association between ISSD and hypertension in a large clinical sample. We studied 348 patients diagnosed with chronic insomnia disorder (CID) based on International Classification of Sleep Disorders (ICSD-3) criteria and 150 normal sleepers. Objective short sleep duration was defined by the median total sleep time (TST) of the sample (< 7 hours) measured with 1-night polysomnography. Hypertension was defined based on blood pressure (BP) levels, antihypertensive medication use and/or a physician diagnosis. Results After adjusting for potential confounders, patients with CID who slept < 7 hours were associated with 2.8-fold increased odds of hypertension compared to normal sleepers who slept ≥7 hours (odds ratio [OR]=2.81, 95% confidence interval [95%CI]=1.068–7.411) or < 7 hours (OR=2.75, 95%CI=1.005-7.542), whereas patients with CID who slept ≥ 7 hours (OR=1.52, 95%CI=0.537-4.285) or normal sleepers who slept < 7 hours (OR=1.07, 95%CI=0.294-3.904) were not significantly associated with increased odds of hypertension compared to normal sleepers who slept ≥ 7 hours. Linear regression analyses showed that, for every hour decrease in TST, systolic and diastolic blood pressure increased by 1.014 mmHg (p=0.045) and 0.923 mmHg (p=0.015), respectively, in patients with CID but not in normal sleepers. Conclusion Our findings further support that ISSD is a risk factor for hypertension and objective short sleep duration may be a useful marker of the biological severity of CID in clinical practice. Support (if any) This study was supported by the National Natural Science Foundation of China (81970087), Guangdong Province Science and Technology Special Fund Project (200115165870512), and the 2020 Li Ka Shing Foundation Cross-Disciplinary Research Grant (2020LKSFG05B). The authors report no conflict of interest.

Funding Acknowledgements Type of funding sources: None. Introduction Coronary Heart Disease (CHD) is the most common type of heart disease and a major cause of mortality worldwide, since according to CDC and WHO, it accounts for 18.2 million cases and 17.9 million deaths annually, respectively. Hypertension can precipitate the condition significantly, thus controlling it plays an important role in the secondary prevention of the disease. Aim The aim of this study is to highlight the significance of hypertension as a risk factor in patients with CAD, as well as, to compare its prevalence to those of the EUROASPIRE IV and the statistics published from the ESC Atlas of Cardiology in 2019. Methods A retrospective, observational study was created, from the Registry of Cyprus Heart Survey, where 375 individuals (88% Males, 66 years old on average) were examined in Nicosia General Hospital Cardiology Clinics with CAD, between the years 2011 and 2014. Their past medical history in regards to hypertension was noted and the data was analyzed by using Microsoft Excel software. Results The total prevalence of hypertension, based on the past medical history of the patients was 59% (females 61% and males 68%). Out of these, 44% still had abnormally elevated blood pressure on their visit to the Cardiology Clinic (females 36% and males 45%). Additionally, the EUROASPIRE IV study showed a prevalence of hypertension of 42.7% and ESC Atlas 24.8%, with median rates 22.3% for females and 27.0% for males. The total mean systolic blood pressure amongst all patients in our study was 136 mmHg, with no significant differences between males and females (136 mmHg and 137 mmHg respectively), while in ESC Atlas, the median SBP levels were noted to be 123.0mmHg in females and 130.0 in males. Conclusion Comparing the results from this group of consecutive patients from the Cyprus Heart Survey to the results of EUROASPIRE IV and ESC, it is made clear that all three studies point to the same conclusion. Firstly, it is important to acknowledge the difference between the two genders, with males recording a higher prevalence of hypertension. Moreover, despite the improvement observed in the management of hypertension that has been noted in our study, the secondary prevention guidelines are still not appropriately met. Managing appropriately hypertension, is of utmost importance in lowering the risk of recurrence of CAD in the context of secondary prevention measures.

Funding Acknowledgements Type of funding sources: None. Background High body mass index (BMI) is a precursor to coronary artery disease (CAD) and an aggravator of the other co-existing CAD risk factors such as diabetes and hypertension. Lifestyle changes (e.g. balanced diet and exercise) in patients with high BMI are usually overlooked, although they contribute positively to prevention and improvement of CAD. Purpose The aim of this study is to calculate the prevalence of overweight and obesity in known CAD patients in both genders, in correlation with diabetes, hypertension, exercise and diet in CAD patients and to compare the findings to EUROASPIRE IV conducted in 2015 (1). Methods This study retrospectively included 362 patients (88% male; mean age 67 years) with a history of CAD (MI, PCI or CABG) from the registry of Cyprus heart survey in a hospital, in Nicosia from 2011 to 2014. Age, gender, date of myocardial infarction event, date of PCI or CABG surgery as well as CAD risk factors such as BMI, exercise, diet, hypertension and diabetes were noted on their visit to the cardiac clinic. Results Our study showed an overall similarity in BMI prevalence across both genders. The prevalence increased from 17.7% in patients with normal BMI (18.5-24.9) to the highest CAD prevalence of 49.2% which was seen in overweight (BMI = 25 –29.9) patients. However, there was a drop in the prevalence of obese (BMI = 30+) patients to 32.9%. This is supported by EUROASPIRE IV (1) which highlighted that CAD prevalence was higher in overweight patients (male = 83%; female = 80%) than obese patients (male = 36%; female = 44%) by nearly 2-fold. Furthermore, within the higher-than-normal BMIs, we recognized more non-diabetic CAD patients (115 overweight; 67 obese) in our study than diabetic CAD patients (62 overweight; 55 obese). On the contrary, hypertensive CAD patients (106 overweight; 80 obese) were more frequent than non-hypertensive CAD patients (71 overweight; 43 obese). Overweight patients split in nearly half when it came to exercise and diet (96 exercise, 82 do not; 90 diet, 88 do not). While in obese patients there was a higher proportion of patients not exercising or following a diet (47 exercise, 72 do not; 32 diet, 87 do not). According to EUROASPIRE IV (1), obesity contributed to higher prevalence of diabetes as patients did not lose weight. Conclusion Overweight and obese patients make up a large percentage of CAD patients. High BMI had a negative additive effect with hypertension but not with diabetes on the risk prevention in CAD patients which mismatches with the EUROASPIRE IV (1) findings. Despite BMI being a modifiable risk factor, not adhering to a diet or exercise was noticed in overweight and obese patients, which in return weakens their prevention of CAD.

Funding Acknowledgements Type of funding sources: None. Background Morbidity and mortality are increased in patients with myocardial infarction that also have co-existing diabetes mellitus (DM) making it an important risk factor for coronary artery disease (CAD). Overall, diabetes mellitus worsens the prognosis in CAD patients. Purpose This paper was done from a study, that enabled us to measure the prevalence of diabetes mellitus in patients with coronary artery disease, in relevance to other CAD risk factors (age, gender, systolic blood pressure, LDL-C and smoking). These results would give us the ability to compare it with the outcomes of the EUROSPIRE IV study published in 2015 (1). Methods Retrospective observational study of consecutive patients from the Registry of Cyprus Heart Survey, examined in the Cardiology Clinic of Nicosia General Hospital, between the years 2011-14. The total number of patients was 371 (11.5% females and 88.4% males). These patients had a history of myocardial infarction and underwent either a PCI or a CABG. Results From the total amount of patients, 36.9% had history of diabetes mellitus. The percentage adjusted to gender shows that 44% of females and 35.6% of males included in the study had diabetes. The mean age of people that had diabetes and coronary artery disease was 68.65 (CI: 67.18, 70.12). The prevalence of diabetics with hypertension and coronary artery disease was 75.91% while the average systolic blood pressure (SBP) was 138 mmHg (CI: 135.33, 140.67). The systolic blood pressure was ≥140 mmHg in half of the diabetic individuals. Smoking was also assessed as a risk factor in patients with diabetes and CAD. The prevalence of ex-smokers was 28.46%, of smokers 18.24% and of non-smokers 53.28%. Finally, values of low density lipoprotein cholesterol (LDL-C) were measured in 90.5% of diabetic patients, 88.7% of them had an LDL-C ≥1.8 mmol/L (≥70mg/dL) and 53.22% had an LDL-C ≥2.5 mmol/L (≥100mg/dL). The average LDL-C value was 109.19 mg/dL. Conclusions The outcome of the study revealed that a substantial number of patients with CAD suffer from diabetes. Therefore, diabetes was verified as a major risk factor in patients with CAD and the development of acute coronary syndrome. Regarding those patients, other risk factors proved to have a negative impact on their cardiovascular health. Moreover, the risk factors in patients with DM and CAD of this study were compared with the well known study, EUROASPIRE IV (1). The prevalence of diabetes in the present study was 36.9%, compared to 26.8% in EUROASPIRE IV, indicating a higher prevalence in our study. We concluded that marked reduction in the events of myocardial infarction can be seen if we reduce the prevalence of uncontrolled diabetes mellitus occurrences with medication or better control of the risk factors of CAD early in the diagnosis to reduce complications.

Genomic rearrangements are known to result in proto-oncogene deregulation in many cancers, but the link to 3D genome structure remains poorly understood. Here, we used the highly predictive heteromorphic polymer (HiP-HoP) model to predict chromatin conformations at the proto-oncogeneCCND1in healthy and malignant B cells. After confirming that the model gives good predictions of Hi-C data for the nonmalignant human B cell–derived cell line GM12878, we generated predictions for two cancer cell lines, U266 and Z-138. These possess genome rearrangements involvingCCND1and the immunoglobulin heavy locus (IGH), which we mapped using targeted genome sequencing. Our simulations showed that a rearrangement in U266 cells where a singleIGHsuper-enhancer is inserted next toCCND1leaves the local topologically associated domain (TAD) structure intact. We also observed extensive changes in enhancer-promoter interactions within the TAD, suggesting that it is the downstream chromatin remodeling which gives rise to the oncogene activation, rather than the presence of the inserted super-enhancer DNA sequence per se. Simulations of theIGH-CCND1reciprocal translocation in Z-138 cells revealed that an oncogenic fusion TAD is created, encompassingCCND1and theIGHsuper-enhancers. We predicted how the structure and expression ofCCND1changes in these different cell lines, validating this using qPCR and fluorescence in situ hybridization microscopy. Our work demonstrates the power of polymer simulations to predict differences in chromatin interactions and gene expression for different translocation breakpoints.

Genomic rearrangements are known to result in proto-oncogene deregulation in many cancers, but the link to genome 3D structure remains poorly understood. Here we used the highly-predictive heteromorphic polymer (HiP-HoP) model to predict chromatin conformations at the proto-oncogene CCND1 in healthy and malignant B-cells. After confirming that the model gives good predictions of Hi-C data for the non-malignant human B-cell derived cell line GM12878, we generated predictions for two cancer cell lines, U266 and Z-138. These possess genome rearrangements involving CCND1 and the immunoglobulin heavy chain locus (IGH), which we mapped using targeted genome sequencing. Our simulations showed that a rearrangement in U266 cells where a single IGH super-enhancer is inserted next to CCND1 leaves the local topologically associated domain (TAD) structure intact. We also observed extensive changes in enhancer-promoter interactions within the TAD, suggesting that it is the downstream chromatin remodelling which gives rise to the oncogene activation, rather than the presence of the inserted super-enhancer DNA sequence per se. Simulations of the IGH-CCND1 reciprocal translocation in Z-138 cells revealed that an oncogenic fusion TAD is created, encompassing CCND1 and the IGH super-enhancers. We predicted how the structure and expression of CCND1 changes in these different cell lines, validating this using qPCR and fluorescence in situ hybridization microscopy. Our work demonstrates the power of polymer simulations to predict differences in chromatin interactions and gene expression for different translocation break-points.

Monoclonal antibodies (mAbs) constitute a promising class of therapeutics, since ca. 25% of all biotech drugs in development are mAbs. Even though their therapeutic value is now well established, human- and murine-derived mAbs do have deficiencies, such as short in vivo lifespan and low stability. However, the most difficult obstacle to overcome, toward the exploitation of mAbs for disease treatment, is the prevention of the formation of protein aggregates. ANTISOMA is a pipeline for the reduction of the aggregation tendency of mAbs through the decrease in their intrinsic aggregation propensity, based on an automated amino acid substitution approach. The method takes into consideration the special features of mAbs and aims at proposing specific point mutations that could lead to the redesign of those promising therapeutics, without affecting their epitope-binding ability. The method is available online at http://bioinformatics.biol.uoa.gr/ANTISOMA .

Chromosomal translocations are important drivers of haematological malignancies whereby proto-oncogenes are activated by juxtaposition with super-enhancers, often called super-enhancer hijacking . We analysed the epigenomic consequences of rearrangements between the enhancers of the immunoglobulin heavy chain locus (IGH) and proto-oncogene CCND1 that are common in B-cell malignancies. By integrating BLUEPRINT epigenomic data with DNA breakpoint detection, we characterised the normal chromatin landscape of the human IGH locus and its dynamics after pathological genomic rearrangement. We detected an H3K4me3 broad domain (BD) within the IGH locus of healthy B-cells that was absent in samples with IGH-CCND1 translocations. The appearance of H3K4me3-BD over CCND1 in the latter was associated with overexpression and extensive chromatin accessibility of this locus. We observed similar cancer-specific H3K4me3-BDs associated with super-enhancer hijacking of other common oncogenes in B-cell ( MAF , MYC and FGFR3 ) and in T-cell malignancies ( LMO2 , TLX3 and TAL1 ). Our analysis suggests that H3K4me3-BDs are created by super-enhancers and supports the new concept of epigenomic translocation , where the relocation of H3K4me3-BDs accompanies the translocation of super-enhancers.