preAssemble: a tool for automatic sequencer trace data processing

BACKGROUND: Trace or chromatogram files (raw data) are produced by automatic nucleic acid sequencing equipment or sequencers. Each file contains information which can be interpreted by specialised software to reveal the sequence (base calling). This is done by the sequencer proprietary software or publicly available programs. Depending on the size of a sequencing project the number of trace files can vary from just a few to thousands of files. Sequencing quality assessment on various criteria is important at the stage preceding clustering and contig assembly. Two major publicly available packages – Phred and Staden are used by preAssemble to perform sequence quality processing. RESULTS: The preAssemble pre-assembly sequence processing pipeline has been developed for small to large scale automatic processing of DNA sequencer chromatogram (trace) data. The Staden Package Pregap4 module and base-calling program Phred are utilized in the pipeline, which produces detailed and self-explanatory output that can be displayed with a web browser. preAssemble can be used successfully with very little previous experience, however options for parameter tuning are provided for advanced users. preAssemble runs under UNIX and LINUX operating systems. It is available for downloading and will run as stand-alone software. It can also be accessed on the Norwegian Salmon Genome Project web site where preAssemble jobs can be run on the project server. CONCLUSION: preAssemble is a tool allowing to perform quality assessment of sequences generated by automatic sequencing equipment. preAssemble is flexible since both interactive jobs on the preAssemble server and the stand alone downloadable version are available. Virtually no previous experience is necessary to run a default preAssemble job, on the other hand options for parameter tuning are provided. Consequently preAssemble can be used as efficiently for just several trace files as for large scale sequence processing

Oligomerization of Dicyclopentadiene Fraction Using Monosubstituted Titanium Chloride as a Catalyst

The purpose of this study is to investigate the dicyclopentadiene fraction of liquid pyrolysis product oligomerization with the use of the modified catalytic system based on titanium alkoxides. The choice of reaction catalyst is specified by searching the ways of obtaining petroleum resins with the improved performance characteristics and the possibility of low-temperature polymerization. The use of monosubstituted titanium chloride as a catalyst allows obtaining light resins, films on the base of which are smooth, glossy and have good technical characteristics: adhesion 1 point, resilience 10 cm

Rationing of medical care: how medical care to be distributed in conditions of limited resources

Background. Rationing of health care—restricting patients’ access to potentially beneficial health care interventions through non-market instruments—is a natural feature of all health care systems as they operate under resource constraints. The purpose of this study is to characterize rationing practices and the attitude of doctors themselves to it, with an emphasis on comparing Russia and the United States and on changes in the perception of rationing during the COVID-19 pandemic. Methods. We conducted a bibliometric analysis of publications in the medical scientific literature since 1989 on the issue of rationing of medical care. To characterize rationing practices in Russia and the United States and the attitudes of doctors towards them, we used data from published studies and data from semi-structured in-depth interviews with 28 Russian doctors. Results. Despite the increasing frequency of publications related to the topic of resource allocation over the past 20 years, studies using the term “rationing” are rare. Both Russia and the USA have practices of explicit and implicit rationing. In Russia they are more diverse and widespread. In both countries, doctors prefer implicit rationing and do not want open discussion of these issues. The practice of rationing is institutionalized. In Russian medical organizations its most common form is a chain of permissions for the use of resources. But most doctors believe they are not rationing care. The pandemic briefly brought the topic of rationing into the public sphere, but then its discussion was limited. The probable reason is that medical practice during the pandemic was carried out within the previous legal framework. Professional organizations have developed several recommendations for rationing, but their usefulness and level of acceptance by professionals and the public is unclear. Conclusions The transition from implicit to explicit rationing is extremely difficult, but is necessary to ensure equitable patient access to scarce medical resources and the effective functioning of health care systems. A major barrier to the explicit and informed use of rationing instrument is the limited public acceptance of it and the reluctance of professional communities to make public decisions that maximize public benefit by prioritizing access to effective interventions

Experience in the use of simultaneous operations in dermatology and cosmetology

Background. Simultaneous (combined, simultaneous) operations are operations in which up to five different surgical procedures are performed simultaneously during one surgical intervention. According to WHO statistics, about a third of all surgical patients need simultaneous operations. A feature of medical interventions in dermatovenereology and cosmetology is the unwillingness and unwillingness of the patient to experience tangible pain discomfort during the procedures. The arsenal of modern cosmetology is constantly replenished with technologies that not only provide convincing clinical effects, but are also capable of provoking a negative psycho-emotional state in a patient who undergoes certain painful manipulations. Aims. To reflect the experience of a private medical organization, which is one of the first in the country to actively introduce simultaneous surgery in dermatology for several years. Materials and methods. Clinical observation, examination results. Results. In 2022, 32 surgical interventions were performed simultaneously with a dermatovenereologist in this clinic. Also, the clinic regularly performs simultaneous operations in the following combinations: hysteroscopy (with or without curettage) + removal of benign melanocytic/non-melanocytic skin tumors; surgical treatment of hemorrhoids + removal of papillomas/nevi; surgical treatment of anal fissure + removal of papillomas/nevi; laser vaporization of the pilonidal sinus + removal of genital warts; laparoscopic cholecystectomy + removal of nevi. Conclusion. The use of simultaneous operations in dermatovenerological practice is economically justified and justified, taking into account the modern possibilities of anesthetic care, improving their technical and medical support. Simultaneous combined operations exclude psycho-emotional experiences of the forthcoming repeated surgical intervention in patients and allow the surgeon to conduct high-quality medical interventions in a comfortable environment

Safety and immunogenicity of rAd26 and rAd5 vector-based heterologous prime-boost COVID-19 vaccine against SARS-CoV-2 in healthy adolescents: an open-label, non-randomized, multicenter, phase 1/2, dose-escalation study

To protect young individuals against SARS-CoV-2 infection, we conducted an open-label, prospective, non-randomised dose-escalation Phase 1/2 clinical trial to evaluate the immunogenicity and safety of the prime-boost “Sputnik V” vaccine administered at 1/10 and 1/5 doses to adolescents aged 12–17 years. The study began with the vaccination of the older cohort (15-to-17-year-old participants) with the lower (1/10) dose of vaccine and then expanded to the whole group (12-to-17-year-old participants). Next, 1/5 dose was used according to the same scheme. Both doses were well tolerated by all age groups. No serious or severe adverse events were detected. Most of the solicited adverse reactions were mild. No significant differences in total frequencies of adverse events were registered between low and high doses in age-pooled groups (69.6% versus 66.7%). In contrast, the 1/5 dose induced significantly higher humoral and T cell-mediated immune responses than the 1/10 dose. The 1/5 vaccine dose elicited higher antigen-binding (both S and RBD-specific) as well as virus-neutralising antibody titres at the maximum of response (day 42), also resulting in a statistically significant difference at a distanced timepoint (day 180) compared to the 1/10 vaccine dose. Higher dose resulted in increased cross-neutralization of Delta and Omicron variants.;Clinical Trial RegistrationClinicalTrials.gov, NCT04954092, LP-007632

Epigenetic inactivation of the splicing RNA-binding protein CELF2 in human breast cancer.

To access publisher's full text version of this article, please click on the hyperlink in Additional Links field or click on the hyperlink at the top of the page marked DownloadHuman tumors show altered patterns of protein isoforms that can be related to the dysregulation of messenger RNA alternative splicing also observed in transformed cells. Although somatic mutations in core spliceosome components and their associated factors have been described in some cases, almost nothing is known about the contribution of distorted epigenetic patterns to aberrant splicing. Herein, we show that the splicing RNA-binding protein CELF2 is targeted by promoter hypermethylation-associated transcriptional silencing in human cancer. Focusing on the context of breast cancer, we also demonstrate that CELF2 restoration has growth-inhibitory effects and that its epigenetic loss induces an aberrant downstream pattern of alternative splicing, affecting key genes in breast cancer biology such as the autophagy factor ULK1 and the apoptotic protein CARD10. Furthermore, the presence of CELF2 hypermethylation in the clinical setting is associated with shorter overall survival of the breast cancer patients carrying this epigenetic lesion.Health Department PERIS-project of the Catalan Government (Generalitat de Catalunya) AGAUR of the Catalan Government (Generalitat de Catalunya) Instituto de Salud Carlos III Ministerio de Economia y Competitividad (MINECO) European Union (EU) Foundation CELLEX La Caixa Foundatio

Care of patients with inborn errors of immunity in thirty J Project countries between 2004 and 2021

IntroductionThe J Project (JP) physician education and clinical research collaboration program was started in 2004 and includes by now 32 countries mostly in Eastern and Central Europe (ECE). Until the end of 2021, 344 inborn errors of immunity (IEI)-focused meetings were organized by the JP to raise awareness and facilitate the diagnosis and treatment of patients with IEI.ResultsIn this study, meeting profiles and major diagnostic and treatment parameters were studied. JP center leaders reported patients’ data from 30 countries representing a total population of 506 567 565. Two countries reported patients from JP centers (Konya, Turkey and Cairo University, Egypt). Diagnostic criteria were based on the 2020 update of classification by the IUIS Expert Committee on IEI. The number of JP meetings increased from 6 per year in 2004 and 2005 to 44 and 63 in 2020 and 2021, respectively. The cumulative number of meetings per country varied from 1 to 59 in various countries reflecting partly but not entirely the population of the respective countries. Altogether, 24,879 patients were reported giving an average prevalence of 4.9. Most of the patients had predominantly antibody deficiency (46,32%) followed by patients with combined immunodeficiencies (14.3%). The percentages of patients with bone marrow failure and phenocopies of IEI were less than 1 each. The number of patients was remarkably higher that those reported to the ESID Registry in 13 countries. Immunoglobulin (IgG) substitution was provided to 7,572 patients (5,693 intravenously) and 1,480 patients received hematopoietic stem cell therapy (HSCT). Searching for basic diagnostic parameters revealed the availability of immunochemistry and flow cytometry in 27 and 28 countries, respectively, and targeted gene sequencing and new generation sequencing was available in 21 and 18 countries. The number of IEI centers and experts in the field were 260 and 690, respectively. We found high correlation between the number of IEI centers and patients treated with intravenous IgG (IVIG) (correlation coefficient, cc, 0,916) and with those who were treated with HSCT (cc, 0,905). Similar correlation was found when the number of experts was compared with those treated with HSCT. However, the number of patients treated with subcutaneous Ig (SCIG) only slightly correlated with the number of experts (cc, 0,489) and no correlation was found between the number of centers and patients on SCIG (cc, 0,174).Conclusions1) this is the first study describing major diagnostic and treatment parameters of IEI care in countries of the JP; 2) the data suggest that the JP had tremendous impact on the development of IEI care in ECE; 3) our data help to define major future targets of JP activity in various countries; 4) we suggest that the number of IEI centers and IEI experts closely correlate to the most important treatment parameters; 5) we propose that specialist education among medical professionals plays pivotal role in increasing levels of diagnostics and adequate care of this vulnerable and still highly neglected patient population; 6) this study also provides the basis for further analysis of more specific aspects of IEI care including genetic diagnostics, disease specific prevalence, newborn screening and professional collaboration in JP countries

Early mobilisation in critically ill COVID-19 patients: a subanalysis of the ESICM-initiated UNITE-COVID observational study

Background Early mobilisation (EM) is an intervention that may improve the outcome of critically ill patients. There is limited data on EM in COVID-19 patients and its use during the first pandemic wave. Methods This is a pre-planned subanalysis of the ESICM UNITE-COVID, an international multicenter observational study involving critically ill COVID-19 patients in the ICU between February 15th and May 15th, 2020. We analysed variables associated with the initiation of EM (within 72 h of ICU admission) and explored the impact of EM on mortality, ICU and hospital length of stay, as well as discharge location. Statistical analyses were done using (generalised) linear mixed-effect models and ANOVAs. Results Mobilisation data from 4190 patients from 280 ICUs in 45 countries were analysed. 1114 (26.6%) of these patients received mobilisation within 72 h after ICU admission; 3076 (73.4%) did not. In our analysis of factors associated with EM, mechanical ventilation at admission (OR 0.29; 95% CI 0.25, 0.35; p = 0.001), higher age (OR 0.99; 95% CI 0.98, 1.00; p ≤ 0.001), pre-existing asthma (OR 0.84; 95% CI 0.73, 0.98; p = 0.028), and pre-existing kidney disease (OR 0.84; 95% CI 0.71, 0.99; p = 0.036) were negatively associated with the initiation of EM. EM was associated with a higher chance of being discharged home (OR 1.31; 95% CI 1.08, 1.58; p = 0.007) but was not associated with length of stay in ICU (adj. difference 0.91 days; 95% CI − 0.47, 1.37, p = 0.34) and hospital (adj. difference 1.4 days; 95% CI − 0.62, 2.35, p = 0.24) or mortality (OR 0.88; 95% CI 0.7, 1.09, p = 0.24) when adjusted for covariates. Conclusions Our findings demonstrate that a quarter of COVID-19 patients received EM. There was no association found between EM in COVID-19 patients' ICU and hospital length of stay or mortality. However, EM in COVID-19 patients was associated with increased odds of being discharged home rather than to a care facility. Trial registration ClinicalTrials.gov: NCT04836065 (retrospectively registered April 8th 2021)