Cladribine tablets for highly active relapsing-remitting multiple sclerosis in Poland: a real-world, multi-centre, retrospective, cohort study during the COVID-19 pandemic

Introduction. Treatment with cladribine tablets is indicated in highly active relapsing-remitting multiple sclerosis (RRMS). Cladribine tablets proved safe and effective in the pivotal CLARITY trial, but that trial included primarily treatment-naïve patients. In clinical practice however, cladribine tablets are often given to patients who have failed other treatments. Therefore, this study investigated the real-world safety and efficacy of cladribine tablets. Material and methods. We gathered data from nine MS clinical centres across Poland for patients with RRMS who started treatment with cladribine tablets from December 2019 to June 2022. Results. We enrolled 140 patients, with follow-up data available for 136 in year 1 and for 66 in year 2. At baseline, the mean age was 35.6 years, mean disease duration was 7.3 years, median EDSS score was 2.5, and 94% of patients were treatment- -experienced. Thirty-nine patients (27.9%) had undergone COVID-19, and 94 (67.1%) were vaccinated against COVID-19. The annualised relapse rate (ARR) decreased from 1.49 at baseline to 0.33 in year 1 (p < 0.001) and to 0.25 in year 2 (p < 0.001). The percentage of relapse-free patients increased from 11.5% at baseline to 70.2% in year 1 and 82.1% in year 2. The percentage of patients with active lesions decreased from 91.4% at baseline to 36.2% in year 1 and 18.2% in year 2. EDSS score remained stable or improved in 83.7% of patients in year 1 and 89.6% in year 2. No evidence of disease activity (NEDA-3) was achieved in 42.7% of patients in year 1 and 66.7% in year 2. Only one patient (0.72%) had grade 4 lymphopenia and 21 (15.1%) had grade 3 lymphopenia. Varicella zoster virus infections occurred in three patients. Eight patients discontinued treatment with cladribine: five due to inefficacy, one due to lymphopenia, and two due to a personal decision. Conclusions. Cladribine tablets proved safe and effective in a real-world cohort of treatment-experienced patients. However, the efficacy measures improved to a lesser extent in our cohort than in the pivotal clinical trial, which is probably due to a higher proportion of treatment-experienced patients in our cohort

The 42nd Symposium Chromatographic Methods of Investigating Organic Compounds : Book of abstracts

The 42nd Symposium Chromatographic Methods of Investigating Organic Compounds : Book of abstracts. June 4-7, 2019, Szczyrk, Polan

Knowledge transfer in international corporations in a remote work environment

Przedmiotem pracy jest transfer wiedzy w korporacjach międzynarodowych w warunkach pracy zdalnej. Głównym celem pracy magisterskiej jest przeprowadzenie badania przy użyciu narzędzia badawczego jakim jest ankieta, w celu zbadania odbioru transferu wiedzyw korporacjach przez pracowników korporacji pracujących zdalnie. Przy pomocy ankiety poddano badaniu odczucia pracowników względem poszczególnych rodzajów transferu wiedzy jawnej i ukrytej, oceny zjawisk związanych z przekazywaniem wiedzy oraz zagadnień odnoszących się do transferu wiedzy pomiędzy współpracownikami. W wyniku przeprowadzonych badań dokonano charakterystyki barier, które pracownicy korporacji napotykają w warunkach pracy zdalnej. Dodatkowo praca wprowadza kontekst pracy stacjonarnej w celu porównania odczuć pracowników korporacji w dwóch trybach pracyi oceny zdalnego trybu pracy względem trybu stacjonarnego. W rezultacie scharakteryzowano transfer wiedzy w pracy zdalnej w korporacjach międzynarodowych poprzez analizę poszczególnych czynników i barier.The subject of the thesis is the transfer of knowledge in international corporations in the remote work environment. The main goal of the master's thesis is to conduct a research using a questionnaire, in order to gain knowledge regarding the reception of knowledge transfer in corporations by employees of corporations working remotely. Using the questionnaire, the employees' feelings towards particular types of explicit and tacit knowledge transfer, the assessment of phenomena related to the transfer of knowledge and issues relating to the transfer of knowledge between colleagues were examined. As a result of the research, the barriers faced by corporate employees in remote work conditions were characterized. In addition, the work introduces the context of stationary work in order to compare the feelings of corporate employees in two modes of work. As a result, the transfer of knowledge in remote work in international corporations was characterized through the analysis of individual factors and barriers

Social media mining in science. Project of application aggregating information on current research interests of scientists

Przedmiotem pracy jest eksploracja danych w mediach społecznościowych w kontekście nauki i zainteresowań badawczych naukowców. Głównym celem pracy licencjackiej jest stworzenie aplikacji służącej do agregacji informacji o aktualnych zainteresowaniach badawczych naukowców z zastosowaniem rozwiązań z zakresu eksploracji danych pochodzących z mediów społecznościowych. Przy pomocy metody analizy i krytyki piśmiennictwa analizie poddano historię rozwoju mediów społecznościowych wraz z cechami zjawisk dotyczących eksploracji danych. Omówiono problem szybkiego narastania ilości danych w Internecie. Scharakteryzowano źródła informacji o zainteresowaniach naukowych w podziale na źródła tradycyjne i elektroniczne oraz przeanalizowano ich możliwe zastosowania i funkcjonalności. W rezultacie wyróżniono korzyści płynące z używania mediów społecznościowych w kontekście wyszukiwania informacji personalnej o naukowcach i ich zainteresowaniach badawczych przy wykorzystaniu poszczególnych źródeł informacji.The subject of the thesis is data mining in social media in the context of science and research interests of scientists. The main purpose of the bachelor thesis is to create an application that aggregates information about current research interests of scientists with application of solutions from the social data mining field of science. Using the method of critical literature review the history of social media development together with the characteristics of phenomena concerning data mining were analyzed. The problem of the rapid increase of the amount of data on the Internet was discussed. The sources of information on scientific interests were characterized, dividing into traditional and electronic sources, and their possible applications and functionalities were analyzed. As a result, the benefits of using social media in the context of searching for personal information about scientists and their research interests with the use of particular sources of information were highlighted

The effect of abiotic elicitors on the production of polyphenols in agitated cultures of Aronia x prunifolia (Marshall) Rehder

Jedną ze znanych strategii w biotechnologii roślin, która może doprowadzić do zwiększenia akumulacji metabolitów wtórnych w roślinnych kulturach in vitro jest elicitacja abiotyczna lub biotyczna. Celem pracy było zbadanie wpływu elicitorów abiotycznych - jasmonianu metylu i chlorku kadmu na akumulację jednej z grup polifenoli – kwasów fenolowych, w kulturach wytrząsanych Aronia x prunifolia. Kultury prowadzono na podłożu Murashige-Skoog, zawierającym 1 mg/L BAP i 1 mg/L NAA przez okres 20 dni. Jasmonian metylu (50 µM) i chlorek kadmu (100 µM) dodawano do kolb hodowlanych w 12 dniu trwania hodowli. Biomasę zbierano po 1, 2, 4, 6 i 8 dniach. W ekstraktach z zebranej w różnych punktach czasowych biomasy metodą HPLC oznaczano zawartość 27 kwasów fenolowych. W ekstraktach stwierdzono obecność 10 związków: kwasu neochlorogenowego, kwasu kaftarowego, kwasu protokatechowego, kwasu 3,4-dihydroksyfenylooctowego, kwasu chlorogenowego, kwasu kryptochlorogenowego, kwasu kawowego, kwasu syryngowego, kwasu izochlorogenowego i kwasu rozmarynowego. W ekstraktach zarówno z biomasy rosnącej w warunkach kontrolnych, jak i poddanej elicitacji, stwierdzono ten sam jakościowy skład kwasów fenolowych. Dominującymi ilościowo związkami były kwas chlorogenowy i kwas izochlorogenowy. Wyniki analiz ilościowych udokumentowały stymulujący wpływ zarówno jasmonianu metylu, jak i chlorku kadmu na produkcję kwasów fenolowych. Całkowita zawartość tych związków wzrastała, odpowiednio 1,59-krotnie i 1,44-krotnie. Również zawartości kwasu chlorogenowego i izochlorogenowego wzrastały po zastosowaniu obu elicitorów, odpowiednio 1,52- i 1,97-krotnie (jasmonian metylu) oraz 1,25- i 1,60-krotnie (chlorek kadmu). Ani dodatek jasmonianu metylu, ani chlorku kadmu nie hamował przyrostów biomasy. Uzyskane wyniki wyraźnie udokumentowały korzystny wpływ testowanych elicitorów abiotycznych na produkcję badanej grupy polifenoli w kulturach wytrząsanych A. x prunifolia.One of the known strategies in plant biotechnology which can enhance secondary metabolite accumulation in plant in vitro cultures is based on abiotic or biotic elicitation. The aim of this work was to examine the effect of abiotic elicitors: methyl jasmonate and cadmium chloride on the accumulation of one group of polyphenols, namely phenolic acids in agitated microshoot cultures of Aronia x prunifolia. The cultures were maintained on Murashige-Skoog medium containing 1 mg/L BAP and 1 mg/L NAAfor 20 days. The elicitors: methyl jasmonate (50 µM) and cadmium chloride (100 µM) were added to culture flasks on the 12th day of culture. Biomass was collected after 1, 2, 4, 6 and 8 days. Extracts from biomass collected at different time points were used for determination of 27 phenolic acids using HPLC. The extracts were found to contain 10 compounds: neochlorogenic acid, caftaric acid, protocatechuic acid, 3,4-dihydroxyphenylacetic acid, chlorogenic acid, cryptochlorogenic acid, caffeic acid, syringic acid, isochlorogenic acid and rosmarinic acid. Extracts of biomass growing in control (non-elicited) and in elicited cultures contained the same composition of phenolic acids. Chlorogenic acid and isochlorogenic acid were the dominating compounds. The results of quantitative analyses documented the stimulating effect of both methyl jasmonate and cadmium chloride on phenolic acid production. The total contents of these compounds increased 1.59 times and 1.44 times, respectively. Also, the contents of chlorogenic acid and isochlorogenic acid rose after the addition of both elicitors, 1.52 and 1.97 times (methyl jasmonate) and 1.25 and 1.60 times (cadmium chloride), respectively. Addition of methyl jasmonate and cadmium chloridedid not suppress biomass growth. The obtained results clearly evidenced a beneficial effect of the tested abiotic elicitors on the production of the studied group of polyphenols in agitated cultures of A. x prunifolia

Can HRV Predict Prolonged Hospitalization and Favorable or Unfavorable Short-Term Outcome in Patients with Acute Ischemic Stroke?

The aim of this study was to assess whether the heart rate variability (HRV) could predict a favorable or unfavorable stroke outcome. The endpoint was based on the National Institutes of Health Stroke Scale (NIHSS). The patient’s health condition was assessed upon discharge from the hospital. An unfavorable stroke outcome was defined as death or NIHSS ≥ 9, while NIHSS < 9 meant a favorable stroke outcome. The studied group consisted of 59 patients with acute ischemic stroke AIS (mean age of 65.6 ± 13.2; 58% were females). An original and innovative non-linear measure was used to analyze HRV. It was based on symbolic dynamics consisting of comparing the “length of the longest words” in the night recording of HRV. “The length of the longest word” meant the longest sequence of identical adjacent symbols possible for a patient. An unfavorable stroke outcome occurred in 22 patients, whereas the majority of patients (37) had a favorable stroke outcome. The average hospitalization time of patients with clinical progression was 29 ± 14 days, and with favorable outcomes was 10 ± 3 days. Patients with long words (more than 150 adjacent RR intervals having the same symbol) were hospitalized no longer than 14 days and they had no clinical progression. The patients with a favorable stroke outcome were characterized by longer words. Our pilot study may be the beginning of work on the development of a non-linear, symbolic method as a predictor of prolonged hospitalization and increased risk of clinical progression in patients with AIS

The Hemisphere of the Brain in Which a Stroke Has Occurred Visible in the Heart Rate Variability

The aim of this study was to assess whether heart rate variability (HRV) could predict which hemisphere of the brain was affected during an acute ischemic stroke (AIS). To achieve this goal, we compared HRV between patients with a right (RH) and left hemispheric (LH) stroke. The studied group consisted of 64 patients with AIS (25 with RH and 39 with LH stroke, with a mean age of 64 &plusmn; 12 and 66 &plusmn; 13, p = 0.3, respectively) using 24 h Holter ECG records at NN intervals performed at a mean of 4.3 &plusmn; 2 days following their AIS. Standard linear methods were used to analyze HRV in the time and frequency domains, as well as nonlinear methods, including sample entropy, detrended fluctuation analysis, and asymmetry measures. Patients with an LH stroke had significantly greater values for sample entropy compared to subjects with an RH stroke (1.31 &plusmn; 0.53 vs. 0.92 &plusmn; 0.46, p = 0.003, Bonferroni-corrected p = 0.033, effect size = 0.8). The LH stroke group also had higher RMSSD (113 &plusmn; 81 vs. 76 &plusmn; 61, p = 0.06), pNN50 (33.35 &plusmn; 28.54 vs. 18.52 &plusmn; 23.75, p = 0.02), and HFnu (48.42 &plusmn; 16.41 vs. 42.66 &plusmn; 17.88, p = 0.11) values, when compared to the RH group, which was possibly related to higher activity in the parasympathetic system in the LH group. Conversely, subjects with RH stroke had higher LFnu (57.34 &plusmn; 17.88 vs. 51.58 &plusmn; 16.41, p-value = 0.11) and LF/HF ratios (2.24 &plusmn; 2.87 vs. 1.68 &plusmn; 2.50, p-value = 0.11), which were likely related to higher activity in the sympathetic nervous system, when compared to the LH stroke group. Our pilot study demonstrated that patients with RH stroke had lower HRV complexity than those with LH stroke, indicating that HRV could be useful in the discrimination of hemispheric involvement in AIS

microRNA Expression Profile in Single Hormone Receptor-Positive Breast Cancers Is Mainly Dependent on HER2 Status—A Pilot Study

Estrogen (ER) and progesterone (PgR) receptors and HER2 are crucial in the assessment of breast cancer specimens due to their prognostic and predictive significance. Single hormone receptor-positive breast cancers are less common and their clinical course is less favorable than ER(+)/PgR(+) tumors. Their molecular features, especially microRNA (miRNA) profiles, have not been investigated to date. Tumor specimens from 36 chemonaive breast cancer patients with known ER and PgR status (18 ER(+)/PgR(&minus;) and 18 ER(&minus;)/PgR(+) cases) were enrolled to the study. The expression of 829 miRNAs was evaluated with nCounter Human v3 miRNA expression Assay (NanoString). miRNAs differentiating between ER/PgR/HER2 phenotypes were selected based on fold change (FC) calculated for the mean normalized counts of each probe in compared groups. The differences were estimated with Student&rsquo;s t-test or Two-Way ANOVA (considering also the HER2 status). The results were validated using The Cancer Genome Atlas (TCGA) dataset. Following quality control of raw data, fourcases were excluded due to low sample quality, leaving 14 ER(+)/PgR(&minus;) and 18 ER(&minus;)/PgR(+) cases. After correction for multiple comparisons, we did not find miRNA signature differentiating between ER(&minus;)/PgR(+) and ER(+)/PgR(&minus;) breast cancers. However, a trend for differing expression (p-value &le; 0.05; FDR &gt; 0.2; ANOVA) in eight miRNAs was observed. The ER(+)/PgR(&minus;) group demonstrated elevated levels of four miRNAs&mdash;miR-30a-5p, miR-29c-3p, miR-141-3p and miR-423-5p&mdash;while the ER(&minus;)/PgR(+) tumors were enriched in another four miRNAs&mdash;miR-514b-5p, miR-424-5p, miR-495-3p, and miR-92a-3p. For one of the miRNAs&mdash;miR-29c-3p&mdash;the association with the ER(+)/PgR(&minus;) phenotype was confirmed in the TCGA cohort (p-value = 0.024; t-test). HER2 amplification/overexpression in the NanoString cohort was related to significant differences observed in 33 miRNA expression levels (FDR &le; 0.2; ANOVA). The association with HER2 status was confirmed in the TCGA cohort for four miRNAs (miR-1180-3p, miR-223-3p, miR-30d-5p, and miR-195-5p). The main differences in miRNA expression amongst single hormone receptor-positive tumors were identified according to their HER2 status. However, ER(+)/PgR(&minus;) cases tended to express higher levels of miRNAs associated with ER-positivity (miR-30a-5p, miR-29c-3p, miR-141-3p), whereas ER(&minus;)/PgR(+) cancers showed elevated levels of miRNAs characteristic for double- and triple-negative tumors (miR-92a-3p, miR-424-5p). Further studies are necessary to comprehensively analyze miRNA signatures characteristic of ER(&minus;)/PgR(+) and ER(+)/PgR(&minus;) tumors