Identification and characterization of non-coding RNAs and their associated proteins involved in cellular stress responses

We have designed two new experimental approaches to overcome limitations of previously established methods. Their usefulness, however, turned out to be limited and we were unable to provide a reliable improvement to existing methodologies. Secondly, we provided an extensive atlas of the transcriptional landscape of MCF-7 cells during the DDR. We employed three different high-throughput RNA sequencing approaches to provide a comprehensive analysis of the transcriptome. Our efforts led to identification of differentially expressed transcripts regardless of their polyadenylation or stability, or towards their presence in existing genome annotations. We have provided a foundation for future functional studies of lncRNAs potentially involved in DDR and investigated four lncRNAs upregulated in this condition in more detail. Thirdly, we have provided a new important insight into regulatory mechanism of DDX3 – a protein, which has been previously reported to associate with lncRNAs and is implicated in both DDR and tumorigenesis. We have described the nature of DDX3-lncRNAs interactions on a transcriptome-wide scale and furthered our understanding of DDX3 mediated regulation of translation. We have determined the global effects of DDX3 depletion on the abundance of mRNAs and their translation efficiency. In combination with the analysis of DDX3-mRNA binding specificity those results show that the protein is required for translation initiation on subset of mRNAs harboring structured 5’ UTRs

Retrospective assessment of the Lung-RADS performance in the Silesian Lung Cancer Screening Pilot Study

Background. A high percentage of false positive results, observed in lung cancer screening studies with low-dose computed tomography (LDCT), caused the modification of radiological assessment methods. According to the International Early Lung Cancer Action Program (IELCAP) all non-calcified nodules with a dimension ≥ 4 mm were considered as positive. Implementation of classification the Lung CT screening Reporting and Data System (Lung-RADS®) recommends additional testing only for nodules ≥ 6 mm, which reduced of false positive results. Methods. We provided a retrospective analysis of 601 LDCT scans, in asymptomatic volunteers of Pilot Silesian Study of Early Lung Cancer Detection, with at least 20 pack-years of cigarette smoking. The analysis of non- and invasive interventions was done. Assessment of nodules according to the Lung-RADS® system was done. Then the percentage of interventions that could be avoided using the Lung-RADS® criteria was estimated. Results. In total, 1016 nodules were identified in 265 participants. The positive result of screening was defined as a presence of solid or part-solid nodule ≥ 5 mm and ≥ 8 mm in the case of a nonsolid nodule in line with the IELCAP protocol. Screening based on the IELCAP protocol resulted in 200 positive results and based on Lung-RADS® in the 116 positives. The frequency of lung cancers among participants with a positive result was 7 of 200 (4.0%) (95% CI: 1.0%, 6.0%) for IELCAP and 7 of 116 (6.0%) (95% CI: 2.7%, 9.3%) for Lung-RADS®. The Lung-RADS® criteria reduced number of non- and invasive procedures by 48.8% and 24.1%, compared to IELCAP protocol. Conclusions. Adopting the Lung-RADS® classification system may reduce harms and improve the efficiency of lung cancer screening programs.xx

Evaluation of Positioning Functionality in ASG EUPOS for Hydrography and Off-Shore Navigation

The paper discusses the ASG EUPOS services. There is presented an assessment of the possibility of using this system selected sites in hydrography and off-shore navigation tasks. Presented and analyzed the experiments were carried out in the port of Gdynia and on the Gulf of Gda?sk. The results obtaining in the work confirm the possibility of the position accuracy guaranteed by ASG EUPOS services. The obtained accuracy greatly exceeds the needs and requirements of coastal navigation and underwater mining and exploration of sea bottom

Loss of heterozygosity (LOH)--implications for human genetic identification.

The aim of this study was assessment of possible effects of loss of heterozygosity on human genetic identification of histolopathogical tissue sections. DNA templates were extracted from tumour tissue specimens excised from oncological patients and from reference blood samples. AmpFlSTR Identifiler PCR Amplification Kit and ABI 310 Genetic Analyzer (Applera) were used to obtain genetic profiles. Frequency of LOH was calculated for respective samples. Fisher's exact test was performed for statistical analysis. Forty-two percent of the 101 cancer cases analysed were found to possess alterations of the microsatellites manifesting with allelic loss. The most frequently altered loci were D3S1358 and D18S51. The alteration was detected in 47% of cases with larynx carcinoma, 44% of cases with uveal melanoma, 60% of cases with cervical cancers, one case of liposarcoma G3 and one case od neurofibrosarcoma. No LOH was found in liposarcoma G1, dermatofibrosarcoma and cystosarcoma protuberans in either primary or recurrent tumours. In benign tumours (lipoma and fibroma) LOH was also absent. During genotyping of DNA extracted from histopathological tissue sections caution should be taken when non-match or exclusion based on few discrepancies is concluded

Single, very low dose (0.03 mg) of recombinant human thyrotropin (rhTSH) effectively increases radioiodine uptake in the I-131 treatment of large nontoxic multinodular goiter

BACKGROUND: Radioiodine therapy (RIT) in patients with large nontoxic multinodular goiter (MNG) recently becomes more common method in comparison to surgery (especially in elderly patients and with contraindications because of severe chronic diseases other systems). Repeatedly low thyroid radioactive iodine uptake (RAIU) decreases effectiveness of RIT or makes it impossible. The recombinant human thyrotropin can increase RAIU and improve the results of RIT. The aim of the study was to assess the influence of a single very low dose (0.03 mg) of rhTSH on RAIU and thyroid function in euthyroid (MNG-EU) and subclinical hyperthyroid (MNG-SC) patients with a large multinodular goiter. MATERIAL AND METHODS: 40 patients (14 male, 26 female, age 57–80 yr) with large non-toxic MNG over 80 grams and with baseline RAIU < 40% were included into the double-blind randomized study and divided into two groups: rhTSH-group and control group. First group received the single intramuscular injection of 0.03 mg rhTSH and the second received placebo. The RAIU were measured 24 and 48 hours after the rhTSH and then all the patients were administered therapeutic doses of I-131. TSH and free thyroxine levels were measured at 1st and 2nd day after the injection of rhTSH and later, at 4 and 8 weeks after the RIT. RESULTS: The mean RAIU increased significantly from 30.44 ± 7.4% to 77.22 ± 8.7% (p < 0.001). There were no statistically significant differences in RAIU between euthyroid (MNG-EU) and subclinically hyperthyroid (MNG-SC) patients. The peak of serum TSH was noticed 24 hours after rhTSH injection and in MNG-EU patients it has remained within normal range, similarly as fT4. In the MNG-SC group the administration of rhTSH resulted in a significant increase in the TSH values after 24 hours, whose mean level slightly exceeded the upper limit of the normal range with normalization at 48 hours. 8 weeks after the RIT, the TSH and fT4 levels did not exceed the normal range and did not differ in a statistically significant way. Conclusions: Even the single very low dose of rhTSH increases the values of RAIU in significant way, in euthyroid and subclinically hyperthyroid patients. The administration of rhTSH is well-tolerated. Neoadjuvant administration of a low dose (0.03 mg) of rhTSH before I-131 seems to be an optimal method of management which may increase the effectiveness of RIT and decrease the exposure of the patients to absorbed doses of ionizing radiation.BACKGROUND: Radioiodine therapy (RIT) in patients with large nontoxic multinodular goiter (MNG) recently becomes more common method in comparison to surgery (especially in elderly patients and with contraindications because of severe chronic diseases other systems). Repeatedly low thyroid radioactive iodine uptake (RAIU) decreases effectiveness of RIT or makes it impossible. The recombinant human thyrotropin can increase RAIU and improve the results of RIT. The aim of the study was to assess the influence of a single very low dose (0.03 mg) of rhTSH on RAIU and thyroid function in euthyroid (MNG-EU) and subclinical hyperthyroid (MNG-SC) patients with a large multinodular goiter. MATERIAL AND METHODS: 40 patients (14 male, 26 female, age 57–80 yr) with large non-toxic MNG over 80 grams and with baseline RAIU < 40% were included into the double-blind randomized study and divided into two groups: rhTSH-group and control group. First group received the single intramuscular injection of 0.03 mg rhTSH and the second received placebo. The RAIU were measured 24 and 48 hours after the rhTSH and then all the patients were administered therapeutic doses of I-131. TSH and free thyroxine levels were measured at 1st and 2nd day after the injection of rhTSH and later, at 4 and 8 weeks after the RIT. RESULTS: The mean RAIU increased significantly from 30.44 ± 7.4% to 77.22 ± 8.7% (p < 0.001). There were no statistically significant differences in RAIU between euthyroid (MNG-EU) and subclinically hyperthyroid (MNG-SC) patients. The peak of serum TSH was noticed 24 hours after rhTSH injection and in MNG-EU patients it has remained within normal range, similarly as fT4. In the MNG-SC group the administration of rhTSH resulted in a significant increase in the TSH values after 24 hours, whose mean level slightly exceeded the upper limit of the normal range with normalization at 48 hours. 8 weeks after the RIT, the TSH and fT4 levels did not exceed the normal range and did not differ in a statistically significant way. Conclusions: Even the single very low dose of rhTSH increases the values of RAIU in significant way, in euthyroid and subclinically hyperthyroid patients. The administration of rhTSH is well-tolerated. Neoadjuvant administration of a low dose (0.03 mg) of rhTSH before I-131 seems to be an optimal method of management which may increase the effectiveness of RIT and decrease the exposure of the patients to absorbed doses of ionizing radiation

Risk factors of pelvic organ prolapsed in women qualified to reconstructive surgery – the Polish multicenter study

To evaluate the prevalence rate of various pelvic floor disorders among patients treated in 8 academic centers in Poland due to pelvic organ prolapse (POP). Results: The mean age of affected women with POP was 61,25 years (median 61), and mean BMI – 27.62 (median – 27.29). 80% of women were menopausal. Mean time of symptoms related to disease was 65,6 months; whereas the time relapsed from first doctor diagnosis of POP to hospital admission was 50.6 months. 97.4% affected women were multiparous. Only 1.21% women with POP were nulliparous. Family history of prolapse was found in 13.4% of patients, whereas familial positive history of urinary incontinence was 10%. Lower urinary tract symptoms (LUTS) among the analyzed group were as follows: frequency – almost 50%, urgency 32.2%, feeling of improper voiding – 29,6% and voiding difficulty – 17.7%. Functional disorders of lower bowel were found in 43% of patients and the most prevalent symptom was constipation (31%), followed by empting difficulty (12%), dyschesia (9%), and urge stool empting (7.7%). Cardiovascular diseases were found among 43% of respondents, whereas pulmonary diseases with chronic coughing were present in 20% of the analyzed population. Subjective POP symptoms reported by women were as follows: feeling of heaviness in lower abdomen – 37.8%, perineal pain – 27.8%, lumbosacral pain – 34.2%, and abdominal pain – 28.4%. Female sexual disorders were reported by 9,8% women and dyspareunia was found in 7.6% of responders. POP was the main reason for sexual abstinence only in 1 out of 10 patients. More than 30% of patients from the study group underwent previously pelvic surgery due to various reasons. POP related quality of life measured by VAS (Visual Analogue Scale) was 61.4 points (median – 60). The most common finding during gynecological examination was cystocele – 96.5%, followed by rectoenterocele – 92.7%, and central defect – 79%. Mean POP quantification was stage III in POP-Q scale. LUTS symptoms (urinary incontinence, urgency and voiding difficulties) were present among 81% of patients whereas lower gastrointestinal disorders (constipation, fecal incontinence, dyschesia) were found in 43% of women affected by POP

GIS w polskiej edukacji wyższej – dyskusja

The idea for this publication was barn in June 2015, during a meeting of Polish teachers involved with Geographic lnformation Systems. The meeting was initiated by the Department of Geoinformation, Faculty of Geographical Sciences, University of Łódź, which received a grant to organize it. The discussion and presentations from academic teachers representing various universities in Poland were very interesting and sometimes heated. it would be advisable for other educators to familiarise themselves with the aspects of GIS education among Polish geographers, foresters, surveyors and other users. The experience of Geoinformation education in Poland is still modest, so the views of people who have been involved at Polish universities with it since the 1990s should be interesting to readers. Geographic lnformation Systems (GIS) – the integration of environmental and climate issues as an important factor for economic development and quality of life – an innovative second-degree studies. Akronim GIS-E-QL: GIS for environment and quality of life. Project objectives: The main aim of the project is to start-up attractive and innovative second­ degree studies – geoinformation in mutual cooperation of the FGS and the FMCS, students education, improving the competence of academic teachers, conference organization, publishing, cooperation with practitioners and establishing contacts with partners from Norway. This aim is consistent with the “Ana lysis of the economy's demand for graduates in key field of strategy in the context of the Europe 2020” 2012 and “Strategy for development of higher education in Poland 2020”, in the field of promoting innovative courses, formed collectively with practitioners, raising awareness of the environment. Joint actions of educators and practitioners, supported the by the strengthening of university's hardware, software and spatial data, will ensure a high quality project. The existing cooperation with practitioners indicate that further training is necessary and they would like to see postgraduates in their institutions. The final beneficiaries of the project will be the students and the academical teaching staff and indirectly the economy of the region. Students who graduate will be the main recipient of the project, the next will be teaching staff who will have contact with the practices and Norwegian partners with similar interests. In broad terms the project will benefit Polish and European economy and environment.The experience of Polish scientists and educators in the GIS has not been as long as mentioned by Michael F. Goodchild who jointly with Ross Newkirk (Goodchild 2006) started the fi rst GIS training course at the University of Western Ontario in Canada in 1975. Discussions on the scope of knowledge included in the GIS have continued at most universities that have offered such classes. In 1988/89, owing to the National Centre for Geographic Information and Analysis (NCGIA), the 3-volume document of over 1000 pages was put together to include curriculums, student materials and other teaching aids. We have good models and we can use them. Meetings and discussions about the GIS education have been and still are regularly held all over the world (Forer P., Unwin D. 1999). When employees of Polish universities were starting to learn the GIS software and possibilities, Morgan J. M., Fleury B., Becker R. A. (1996) had already identifi ed over 800 higher education institutions all over the world that had offered at least one GIS course. The rapid development of new technologies, methods, the creation of new labour markets has arisen discussions on the contents GIS training in various centres of higher education, e.g. in the Netherlands, the US, and those have been similar to the ones presented in this article (Toppen F. J. 1992) and some issues needed to be resolved in court (DiBiase, D. 2008). You can see how important these meetings of educators are for exchanging opinions and experience. They have allowed to meed people representing various fi elds involved in the geoinformation, which may result in co-operation and new educational initiatives, and sometimes, competition. Finally, we should agree with prof. J. Gaździcki (2009 p. 12) that “It is obvious that the success of any measures to modernise education in the area under consideration depends on the interest of academic communities, involvement of research and academic staff in these endeavours, their will, ambition and willingness to co-operate”.This book has been prepared within the project „Geographic Information Systems (GIS) – the integration of environmental and climate issues as an important factor of economic development and quality of life – an innovative second-degree studies” supported by a grant from Norway through the Norway Grants and co-financed by the Polish funds. (Agreement No FSS/2014/HEI/W/0114/U/0013)

Global burden of 288 causes of death and life expectancy decomposition in 204 countries and territories and 811 subnational locations, 1990–2021: a systematic analysis for the Global Burden of Disease Study 2021

BACKGROUND Regular, detailed reporting on population health by underlying cause of death is fundamental for public health decision making. Cause-specific estimates of mortality and the subsequent effects on life expectancy worldwide are valuable metrics to gauge progress in reducing mortality rates. These estimates are particularly important following large-scale mortality spikes, such as the COVID-19 pandemic. When systematically analysed, mortality rates and life expectancy allow comparisons of the consequences of causes of death globally and over time, providing a nuanced understanding of the effect of these causes on global populations. METHODS The Global Burden of Diseases, Injuries, and Risk Factors Study (GBD) 2021 cause-of-death analysis estimated mortality and years of life lost (YLLs) from 288 causes of death by age-sex-location-year in 204 countries and territories and 811 subnational locations for each year from 1990 until 2021. The analysis used 56 604 data sources, including data from vital registration and verbal autopsy as well as surveys, censuses, surveillance systems, and cancer registries, among others. As with previous GBD rounds, cause-specific death rates for most causes were estimated using the Cause of Death Ensemble model-a modelling tool developed for GBD to assess the out-of-sample predictive validity of different statistical models and covariate permutations and combine those results to produce cause-specific mortality estimates-with alternative strategies adapted to model causes with insufficient data, substantial changes in reporting over the study period, or unusual epidemiology. YLLs were computed as the product of the number of deaths for each cause-age-sex-location-year and the standard life expectancy at each age. As part of the modelling process, uncertainty intervals (UIs) were generated using the 2·5th and 97·5th percentiles from a 1000-draw distribution for each metric. We decomposed life expectancy by cause of death, location, and year to show cause-specific effects on life expectancy from 1990 to 2021. We also used the coefficient of variation and the fraction of population affected by 90% of deaths to highlight concentrations of mortality. Findings are reported in counts and age-standardised rates. Methodological improvements for cause-of-death estimates in GBD 2021 include the expansion of under-5-years age group to include four new age groups, enhanced methods to account for stochastic variation of sparse data, and the inclusion of COVID-19 and other pandemic-related mortality-which includes excess mortality associated with the pandemic, excluding COVID-19, lower respiratory infections, measles, malaria, and pertussis. For this analysis, 199 new country-years of vital registration cause-of-death data, 5 country-years of surveillance data, 21 country-years of verbal autopsy data, and 94 country-years of other data types were added to those used in previous GBD rounds. FINDINGS The leading causes of age-standardised deaths globally were the same in 2019 as they were in 1990; in descending order, these were, ischaemic heart disease, stroke, chronic obstructive pulmonary disease, and lower respiratory infections. In 2021, however, COVID-19 replaced stroke as the second-leading age-standardised cause of death, with 94·0 deaths (95% UI 89·2-100·0) per 100 000 population. The COVID-19 pandemic shifted the rankings of the leading five causes, lowering stroke to the third-leading and chronic obstructive pulmonary disease to the fourth-leading position. In 2021, the highest age-standardised death rates from COVID-19 occurred in sub-Saharan Africa (271·0 deaths [250·1-290·7] per 100 000 population) and Latin America and the Caribbean (195·4 deaths [182·1-211·4] per 100 000 population). The lowest age-standardised death rates from COVID-19 were in the high-income super-region (48·1 deaths [47·4-48·8] per 100 000 population) and southeast Asia, east Asia, and Oceania (23·2 deaths [16·3-37·2] per 100 000 population). Globally, life expectancy steadily improved between 1990 and 2019 for 18 of the 22 investigated causes. Decomposition of global and regional life expectancy showed the positive effect that reductions in deaths from enteric infections, lower respiratory infections, stroke, and neonatal deaths, among others have contributed to improved survival over the study period. However, a net reduction of 1·6 years occurred in global life expectancy between 2019 and 2021, primarily due to increased death rates from COVID-19 and other pandemic-related mortality. Life expectancy was highly variable between super-regions over the study period, with southeast Asia, east Asia, and Oceania gaining 8·3 years (6·7-9·9) overall, while having the smallest reduction in life expectancy due to COVID-19 (0·4 years). The largest reduction in life expectancy due to COVID-19 occurred in Latin America and the Caribbean (3·6 years). Additionally, 53 of the 288 causes of death were highly concentrated in locations with less than 50% of the global population as of 2021, and these causes of death became progressively more concentrated since 1990, when only 44 causes showed this pattern. The concentration phenomenon is discussed heuristically with respect to enteric and lower respiratory infections, malaria, HIV/AIDS, neonatal disorders, tuberculosis, and measles. INTERPRETATION Long-standing gains in life expectancy and reductions in many of the leading causes of death have been disrupted by the COVID-19 pandemic, the adverse effects of which were spread unevenly among populations. Despite the pandemic, there has been continued progress in combatting several notable causes of death, leading to improved global life expectancy over the study period. Each of the seven GBD super-regions showed an overall improvement from 1990 and 2021, obscuring the negative effect in the years of the pandemic. Additionally, our findings regarding regional variation in causes of death driving increases in life expectancy hold clear policy utility. Analyses of shifting mortality trends reveal that several causes, once widespread globally, are now increasingly concentrated geographically. These changes in mortality concentration, alongside further investigation of changing risks, interventions, and relevant policy, present an important opportunity to deepen our understanding of mortality-reduction strategies. Examining patterns in mortality concentration might reveal areas where successful public health interventions have been implemented. Translating these successes to locations where certain causes of death remain entrenched can inform policies that work to improve life expectancy for people everywhere. FUNDING Bill & Melinda Gates Foundation