Machine Learning Analyzed Weather Conditions as an Effective Means in the Predicting of Acute Coronary Syndrome Prevalence.

Background: The prediction of the number of acute coronary syndromes (ACSs) based on the weather conditions in the individual climate zones is not effective. We sought to investigate whether an artificial intelligence system might be useful in this prediction. Methods: Between 2008 and 2018, a total of 105,934 patients with ACS were hospitalized in Lesser Poland Province, one covered by two meteorological stations. The predicted daily number of ACS has been estimated with the Random Forest machine learning system based on air temperature (°C), air pressure (hPa), dew point temperature (Td) (°C), relative humidity (RH) (%), wind speed (m/s), and precipitation (mm) and their daily extremes and ranges derived from the day of ACS and from 6 days before ACS. Results: Of 840 pairwise comparisons between individual weather parameters and the number of ACS, 128 (15.2%) were significant but weak with the correlation coefficients ranged from -0.16 to 0.16. None of weather parameters correlated with the number of ACS in all the seasons and stations. The number of ACS was higher in warm front days vs. days without any front [40 (29-50) vs. 38 (27-48), respectively, P < 0.05]. The correlation between the predicted and observed daily number of ACS derived from machine learning was 0.82 with 95% CI of 0.80-0.84 (P < 0.001). The greatest importance for machine learning (range 0-1.0) among the parameters reached Td daily range with 1.00, pressure daily range with 0.875, pressure maximum daily range with 0.864, and RH maximum daily range with 0.853, whereas among the clinical parameters reached hypertension daily range with 1.00 and diabetes mellitus daily range with 0.28. For individual seasons and meteorological stations, the correlations between the predicted and observed number of ACS have ranged for spring from 0.73 to 0.77 (95% CI 0.68-0.82), for summer from 0.72 to 0.76 (95% CI 0.66-0.81), for autumn from 0.72 to 0.83 (95% CI 0.67-0.87), and for winter from 0.76 to 0.79 (95% CI 0.71-0.83) (P < 0.001 for each). Conclusion: The weather parameters have proven useful in predicting the prevalence of ACS in a temperate climate zone for all the seasons, if analyzed with an artificial intelligence system. Simultaneously, the analysis of individual weather parameters or frontal scenarios has provided only weak univariate relationships. These findings will require validation in other climatic zones.

Variability of growing degree days in Poland in response to ongoing climate changes in Europe.

An observed increase in air temperature can lead to significant changes in the phenology of plants and, consequently, changes in agricultural production. The aim of the study was to evaluate the spatial differentiation of thermal resources in Poland and their variability during a period of changing thermal conditions in Europe. Since the variability of thermal conditions is of paramount importance for perennial crops, the study focused on apple, plum, and cherry orchard regions in Poland. The analysis was conducted for the period of 1951-2010 using air temperature daily data. Thermal resources have been defined using the growing degree days (GDD) index calculated independently for the whole year and during in frost-free season for three air temperature thresholds: 0, 5, and 10 °C, which determine the non-winter period, growing season, and the period of full plant growth, respectively. In addition, due to the high significance for perennials in particular, the incidence and intensity of frost during flowering were calculated. In this study, a detailed analysis of the spatial differentiation of thermal resources was first performed, followed by an evaluation of long-term variability and associated change patterns. The obtained results confirmed an increase in thermal resources in Poland as a consequence of the lengthening of the growing season. However, the frequency and intensity of spring frost, especially during flowering or even during ripening of plants, remain a threat to harvests in both the eastern and western parts of the country.

Promoter methylation and expression levels of selected hematopoietic genes in pediatric B-cell acute lymphoblastic leukemia.

BACKGROUND: Precursor B-cell acute lymphoblastic leukemia (B-cell ALL) is the most common neoplasm in children and is characterized by genetic and epigenetic aberrations in hematopoietic transcription factor (TF) genes. This study evaluated promoter DNA methylation and aberrant expression levels of early- and late-acting hematopoietic TF genes homeobox A4 and A5 (HOXA4 and HOXA5), Meis homeobox 1 (MEIS1), T-cell acute lymphocytic leukemia 1 (TAL1), and interferon regulatory factors 4 and 8 (IRF4 and IRF8) in pediatric B-cell ALL. METHODS: Blood samples of 38 ALL patients and 20 controls were obtained. DNA was treated with sodium bisulfite and DNA methylation level of HOXA4, HOXA5, MEIS1, TAL1, IRF4, and IRF8 was assessed using quantitative methylation-specific polymerase chain reaction (PCR). Relative gene expression was measured using quantitative reverse transcription-PCR. RESULTS: Aberrant methylation of TAL1, IRF8, MEIS1, and IRF4 was observed in 26.3%, 7.9%, 5.3%, and 2.6% patients, respectively, but not in controls. HOXA4 and HOXA5 were methylated in some controls and hypermethylated in 16% and 5% patients, respectively. IRF8, MEIS1, and TAL1 expression was lower in patients than in controls. MEIS1 expression was inversely correlated with white blood cell (WBC) count. HOXA4 expression was down-regulated in patients with high risk according to the National Cancer Institute (NCI) classification. TAL1 methylation was slightly elevated in patients aged >9 years and in patients showing relapse, suggesting its potential prognostic value. CONCLUSION: Aberrant methylation and expression of the selected hematopoietic genes were correlated with demographic/clinical prognostic factors of pediatric ALL, such as age, WBC count, and NCI risk classification.

TET2 Promoter DNA Methylation and Expression Analysis in Pediatric B-cell Acute Lymphoblastic Leukemia.

TET2 is a novel tumor suppressor gene involved in several hematological malignancies of myeloid and lymphoid origin. Besides loss-of-function mutations and deletions, hypermethylation of the CpG island at the TET2 promoter was found in human cancer. Previous analysis revealed no TET2 mutations in acute lymphoblastic leukemia (ALL). Since the TET2 promoter methylation status in pediatric ALL has not been reported, the aim of the present study was to determine if promoter hypermethylation may be a mechanism of TET2 inactivation in a group of pediatric ALL cases. Methylation of TET2 promoter region in one (1/45) ALL B-common patient was detected by methylation specific polymerase chain reaction (PCR) and subsequently analyzed by bisulfite sequencing. We found no correlation between promoter methylation and gene expression, measured by quantitative reverse transcriptase-PCR, however the level of TET2 expression in ALL group was significantly decreased compared to children's normal peripheral blood mononuclear cells and isolated B-cells. TET2 promoter hypermethylation seems to have limited clinical relevance in childhood B-cell ALL due to its low frequency.

[Preliminary results of the use of MRD test among children with acute lymphoblastic leukaemia]. / Wstepne wyniki wykorzystania testu MRD u dzieci z ostra bialaczka limfoblastyczna.

UNLABELLED: The purpose of the study was to monitor minimal residue disease (MRD) among children with ALL and to evaluate the possibility of using this test to detect and monitor the minimal residual disease (MRD test) in the stratification of risk groups on a parallel basis with other recognised prognostic factors. MATERIALS AND METHODS: 56 children, with de novo diagnosed ALL, comprised test group. Control group consisted of 10 healthy persons. DNA was isolated from peripheral blood and bone marrow. During research applied was the PCR method with the use of starters specific for conservative IgH and TCR delta gene fragments. ALL therapy was monitored by evaluation of MRD in the 15th and 33rd day of treatment and prior to supportive treatment. Stratification into risk groups, based on the MRD test results was compared with the stratification conducted in accordance with the recognised prognostic factors, such as: primary leucocytosis, steroid therapy response, drug resistance and karyotype. RESULTS: Among 52 children (92.8%) of the 56, which were tested prior to the start of treatment, obtained the sought for rearrangement, 90-120bp size stripe being an amplified regrouping of the VDJ fragment. Among all the tested healthy persons, the test result was negative. Testing the IgH and TCR delta gene regrouping allowed to demonstrate clonality of the neoplastic process during the diagnosis in 92.8% of the cases. In some of them the regrouping had a bi- or oligoclonal character. The number of patients with a positive MRD test result was dependent on the phase of treatment. Positive results were recorded among 10% of the patients (4/39) during clinical remission, among 86% (6/7) deceased and among 80% (4/5) suffering from relapse. Among 16.7% (2/13) of the patients with determined relapse or who died due to the course of illness process were also observed negative MRD test results. Steroid resistance was stated among 18/56 children, out of which 8/56 obtained a positive MRD test result in the 33rd day of treatment. Among 3 of them the result was maintained prior to supportive treatment. Leucocytosis during diagnosis above 50 thousand was recorded among 10/56 patients. Among 5 of them determined was rearrangement on the 33rd day of treatment, and for 1 prior to supportive treatment. Cytogenetic tests showed a correct karyotype for 19 out of 56 tested children. In this group steroid resistance was determined among 8 children, high preliminary leucocytosis among 5 and in 17 cases of the tested rearrangement. Stratification into therapeutic groups based on classical prognostic factors in most cases was the same with the stratification based on the MRD test results. The accuracy of the latter method was greater. CONCLUSIONS: The use of MRD test has its application in risk group qualification. MRD test is helpful in determining relapses prior to the appearance of clinical symptoms. Among the tested group of children with ALL a positive MRD test result was a bad prognostic factor. It seams that the use of a combined analysis of the risk factors and the MRD test results in a significant manner contribute to a more complex evaluation of the patient's condition.

[Evaluation of systolic and diastolic function of the left ventricle in children with acute lymphoblastic leukaemia before treatment]. / Ocena czynnosci skurczowej i rozkurczowej lewej komory serca u dzieci z ostra bialaczka limfoblastyczna przed rozpoczeciem leczenia.

Between 1995 and 2001 echo-cardiography was performed in 244 children (128 boys, 116 girls) with acute lymphoblastic leukaemia (ALL) before the beginning of therapy with anthracyclines (medium 5.4 days after the diagnosis). The mean age at diagnosis was 5.4 years (range 9 months to 17.7 years). 189 children (97 boys and 92 girls) were included into the standard and medium risk groups and 55 (31 boys and 24 girls) into the high risk group. 29% of ALL children had disturbances in ECG. Changes in the thickness of the intraventricular septum (%IVSTh) and left ventricular posterior wall (%LVPWTh) were statistically lower, especially in children under 7 years of age. Some children showed lowering of shortening fraction (%FS - 8.6%), ejection fraction (%EF - 10.2%) and corrected velocity of fibber-shortening (Vcfc - 25.8%). Children with decreased shortening fraction (%FS) had left ventricular posterior wall thickness (%LVPWTh) impairment. Changes in diastolic function indicate impaired relaxation and compliance of the left ventricle. Decreased peak early filling velocity (E) was found. There were also longer deceleration time (EDecT) and decreased deceleration from peak E velocity (E/Dec) and longer isovolumetric relaxation time in children in standard and medium risk groups. Shorter acceleration time (EAccT) was seen in the high risk group. Evaluation of cardiac function before anthracycline chemotherapy will allow to select patients with pre-existing cardiac impairment for whom cardioprotective treatment is absolutely necessary.

[5- year old boy with Weber-Christian Syndrome or histiocytic cytophagic panniculitis? Diagnostic difficulties. Case presentation]. / Zespól Webera-Christiana czy histiocytic cytophagic panniculitis u 5-letniego chlopca. Trudnosci diagnostyczne. Opis przypadku.

The aim of the paper is to present a case of a 5-year-old boy hospitalised because of recurrent high temperature and reddish blue infiltration of skin and hypodermis lasting 3 months. Because of pancytopenia and hepatomegaly, we suspected a proliferative disease of the haematopoietic or lymphatic system. Several bone marrow biopsies, did not show neoplastic changes. Serological tests excluded virus and animal borne infections. In the histopathologic examination of skin and hypodermis biopsy there was an inflammatory infiltration of the adipose tissue without features of vessel inflammation (the Weber-Christian syndrome). Al though steroid therapy was applied, the infiltration of the adipose tissue did not regress, while liver dysfunction symptoms intensified and pancytopenia and fever continued. The patient died with symptoms or respiratory and circulatory failure. This case of a 5-year-old boy is presented because of extreme diagnostic difficulties, which occurred at each phase of investigations. The repeated tests, as well as several verifications of the sampled histopathological material did not bring any unequivocal proof of the postulated diagnosis.