bluuebunny/crossref_metadata_2025 huggingface dataset:
„Die Menschenwürde ist unantastbar“ – auch im Gefängnis
Authors: KRETSCHMER Joachim
Published: July 2023

„Alle Personen, denen die Freiheit entzogen ist, sind unter Achtung ihrer Menschenrechte zu behandeln“.1 So lautet Nr. 1 der Grundprinzipien der Europäischen Strafvollzugsgrundsätze des Europarates von 2020.

Es ist eine rechtsstaatliche Selbstverständlichkeit in einem liberalen Verfassungs- und Rechtsstaat, dass die Menschenwürde und die Menschenrechte auch in den Justizvollzugsanstalten = Gefängnissen eines Staates gelten und von den staatlichen Stellen geachtet werden. Auch Strafgefangene und sonstige Personen in anderen Formen des Freiheitsentzugs sind Bürger und Bürgerinnen. Es bedurfte aber 1972 eines Urteils des Bundesverfassungsgerichts (=BVerfG) in Karlsruhe, damit sich diese rechtsstaatliche Selbstverständlichkeit in Gesetzgebung und in der Rechtspraxis durchsetzt.
Nilai-Nilai Kepemimpinan dalam Mengelola Organisasi Sekolah Di SMK Maarif NU Pangandaran
Authors: Ruda’i Muhamad
Published: July 2023

Nilai-nilai kepemimpinan dapat dilihat dari kecerdasan, keyakinan diri, ketekunan integritas, kemampuan dan kecerdasan emosional. Gaya kepemimpinan dalam sebuah organisasi juga beragam. Tujuan dari penelitian ini adalah untuk mengetahui bagaimana penerapan nilai-nilai kepemimpinan dan gaya kepemimpinan yang diterapkan oleh organisasi sekolah di SMK Maarif NU Pangandaran. Metode penelitian ini menggunakan pendekatan kualitatif melalui studi kasus yang ada di lokasi penelitian. Proses pengumpulan data dilakukan dengan wawancara dengan pengurus organisasi sekolah, pelajar, dan pihak guru. Berdasarkan penelitian ini, disimpulkan bahwa penerapan gaya kepemimpinan di SMK Maarif NU Pangandaran menggunakan gaya kepemimpinan demokratis. Selain itu, tampak bahwa nilai-nilai kepemimpinan sangat kental diterapkan di organisasi ini.
Industry Feedback on the Work performance of NEUST Advance Higher Education Graduates
Authors: Gutierrez Manuela
Published: July 2023

An academic institution may have a splendid statement of vision and mission, may have the best curriculum, may have offered the best laboratory, library, and student services as well as may have state of the art facilities and equipment; but still, how their graduates perform outside the school particularly at work shall be the ultimate measure of the quality of education that the school provides.NEUST is one University with a very noble vision and mission. It continuously seeks to improve its operations, processes, and procedures to ensure that it will surely realize its vision and mission. It has even gone as far as forming local and international linkages, venturing into researches, sending faculty to scholarship and training, curriculum revision, and so forth. Indeed, it seems that the only thing yet left for it to do is determine how the graduates perform outside the school, particularly at work. However, such cannot be determined unless a study is made. It is for this reason that this tracer study is conducted.
This is a simple descriptive survey facilitated by the internet's social networking services. Sources of data were 35 industry heads purposively chosen based on having employees who graduated from the NEUST Graduate School and their willingness to participate as respondents in this research undertaking.
Students’ Survival Rate at the Master of Science in Information Technology of NEUST
Authors: Gutierrez Manuela , Dela Cruz Arnold
Published: July 2023

This study is a brief analysis of the survival rate of students taking up MSIT from NEUST Graduate School. This was conducted in August 2020 to determine students’ survival trend while at the same time probing on the possible factors underlying such trend as basis for planning. Specifically, this was conducted to determine 1) the survival trend of students enrolled in the program, and 2) the reasons behind the trend, as well as to identify appropriate course of action that may be recommended based on the results of the analysis. Survival rate was computed based on Cohort’s computations, which is T1 over T2 multiplied by 100 while the data for the second objective were taken from the participants responses to the question “Why did you not continue your MSIT studies”. Participants in the study were students enrolled for the first time in the program from 2015 to 2019. They were purposively chosen on the basis of their not continuing their MSIT course. Out of the target 175 students, only 70 or 40% responded to the e-mailed interview question. This 70 officially became the respondents of the study.
Alignment of Alternative Delivery Modes of Learning for Graduate School Students: Based on Learner Internet Connectivity and Access to Devices
Authors: Cruz Jocelyn , Mangansat Nancy Joy , Damaso Irene
Published: July 2023

This preliminary study aimed to characterize the profile of the graduate school students of Nueva Ecija University of Science and Technology based on access to educational devices and internet connectivity. These were used as a basis for determining the appropriate alternative mode of delivery of education for graduate school students. Descriptive design was utilized with frequency and percentage as descriptive tools. The participants were 847 students from the different programs of the Graduate School and a survey instrument was administered through social media and google form platforms. Results showed that majority of the graduate students have access to educational devices, however, they only had weak internet access. Based on these characteristics, Blended Teaching and Learning, specifically Face-to-Face (F2F) and Remote Teaching and Learning (RTL) through a combination of offline and online instructional materials and asynchronous and synchronous learning activities can be prescribed. However, when broken down per program, it was found that majority of the students under the Doctor of Education-Major in Industrial-Technological Education, Doctor of Philosophy in Engineering Management, Doctor of Philosophy in Educational Management, Doctor of Philosophy in Public Administration, and Doctor of Philosophy in Business Administration programs have full internet access and access to educational devices, which would suggest that Blended Learning and Teaching using F2F + RTL (Online Synchronous Activities) model will be appropriate. Additionally, students enrolled under the remaining programs of Doctor of Philosophy in Science Education, Doctor of Philosophy in Mathematics Education, Master of Science in Information Technology, Master of Arts in English-Major in Applied Linguistics, Master of Arts in Teaching-Major in Vocational-Technological Education, Master of Arts in Teaching-Major in Physics, Master of Arts in Teaching-Major in Science, Master of Arts in Teaching-Major in Mathematics, Master of Engineering Management, Master of Education Management, Master of Public Administration, and Master of Business Administration programs, the majority have a weak internet connection but have access to educational devices which means that Face-to-Face (F2F) and Remote Teaching and Learning (RTL) may be recommended for use.
Instructional Module in Animation for Senior High School Students in Nueva Ecija
Authors: Pasion Billie Jack , Domingo Melessa
Published: July 2023

This study aimed to develop an Instructional Module in Animation for Senior High School Students in Nueva Ecija to aid senior high school students taking the Animation course and teachers with the same discipline. Due to the growth of Animation industry and the newly implemented Animation course in the K to 12 curriculums, the researchers aimed to fill the gap between the demand in entering the course and the instructional materials to help the students who are in this program. The researchers utilized the Input-Process-Output model in developing the module. Specifically, the researchers described the developed module under the following factors: Analysis, Design and Development. Furthermore, they sought the help of thirteen (13) respondents to validate and evaluate the overall acceptability of the developed module in terms of Objectives, Content, Format and Language, Presentation and Usefulness. Moreover, they tested if there were differences among experts’ and teachers’ evaluation. Design and Development method of research was utilized in making this research and expert purposive sampling was used to identify the respondents. Results showed that majority of the respondents strongly agreed that the Objectives, Content, Format and Language, Presentation and Usefulness of the module were highly acceptable. However, there was a significant difference between the evaluation of the teacher and industry expert respondents. In conclusion, the module developed was highly acceptable but the researchers recommended the updating the module once in a while.
Development and Assessment of Web Application for Industrial Technological Education
Authors: Pasion Billie Jack
Published: July 2023

This research developed a Web Application for Industrial Technological Education (WAITE) as online platform for undergraduate and graduate studies. It followed the Analysis, Design, Development, Implementation, and Evaluation (ADDIE) model. The following is a summary of the study's findings: 1. the WAITE was planned based on the needs of teachers and students of flexible learning; 2. the researcher designed the WAITE’s context diagram and use-case scenario as well as to considered the device, internet connectivity and available web browser of the users; 3. in the development, the researcher utilized Notepad++ software as the text editor of PHP and for the database is MySQL which is incorporated on XAMPP application.; 4. in terms of implementation and evaluation, the researcher gathered IT professionals, teachers, and students to test its technical characteristics and instructional use respectively, they gave the WAITE a very high rating. The positive comments and suggestions given by the respondents show the endorsement of this scrupulous niche for the use of technology in pedagogy.
نماذج من التشريعات النبوية في حماية الأطفال من الانحرافات
Authors: الغشيمي د. عبدالواسع محمد غالب
Published: July 2023

هدف البحث إلى بيان بعض التشريعات النبوي التي لها الأثر في حماية الأطفال من الانحراف، المتمثلة بعناية النبي صلى الله عليه وسلم بتعليم الأطفال، وتربيتهم، وتوجيههم والرأفة بهم، والتأكيد على حقوقهم، وحثه صلى الله عليه وسلم على رعاية الأيتام وكفالتهم. ودفع الآباء والمربين إلى الاستفادة من المنهج النبوي في القيام بمهمتهم الجليلة في تربية الأطفال، وقد توصل البحث إلى ضرورة اهتمام الآباء والمربين بتربية الأطفال وتنشئتهم على وفق ما جاءت به التشريعات الإسلامية حتى يكونوا أفرادا صالحين في المجتمع، وسد حاجاتهم من الطعام والشراب والعلاج ووسائل الترفيه المختلفة لكي لا يصبحوا عرضة للانحراف. ويجب على الآباء حسن معاملة أطفالهم والتعامل معهم بروح الشفقة والرحمة؛ لأن الشدة والقسوة الزائدة على سلوكهم وتصرفاتهم تدفعهم إلى مغادرة البيت، فتتلقفهم أيادي السوء، واستغلال ظاهرة الفراغ لدى الاطفال وخاصة في سن المراهقة وشغلها ببرامج علمية ونشاطات متنوعة.
السمات النفسية والاجتماعية المفضلة في عضو هيئة التدريس لدى عينة من طلبة كلية التربية بجامعة تعز
Authors: المخلافي د. صادق عبده سيف
Published: July 2023

هدفت الدراسة إلى الكشف عن السمات النفسية والاجتماعية الأكثر تفضيلا في عضو هيئة التدريس، لدى عينة من طلاب كلية التربية، والتعرف على وجود فروق في السمات النفسية والاجتماعية المفضلة في عضو التدريس لدى أفراد العينة وفقًا للنوع والمستوى العلمي؛ ولهذا الغرض طبق استبيان من إعداد الباحث على عينة قوامها (122) طالبا وطالبة، وتوصل البحث إلى أن سمات الثقة بالنفس: الصدق في تنفيذ الوعود والعدل في التعامل مع الطلاب، والشجاعة في قول الحقيقة، وسعة الصدر، وقد احتلت مركز الصدارة على قائمة السمات المفضلة في عضو هيئة التدريس من وجهة نظر أفراد العينة, واختلاف ترتيب السمات النفسية والاجتماعية لدي أفراد العينة تبعا للجنس والمستوى الدراسي، ووجود فروق ذات دلالة إحصائية بين الذكور والإناث في السمات النفسية والاجتماعية المفضلة لديهم في عضو هيئة التدريس، ووجود فروق ذات دلالة إحصائية في السمات النفسية والاجتماعية المفضلة في عضو هيئة التدريس لدى طلاب أفراد العينة وفقا للمستوى الدراسي.
NEURAL NETWORKS FOR SOLVING HUXLEY’S EQUATION
Authors: Milićević Bogdan , Ivanović Miloš , Stojanović Boban , Filipović Nenad
Published: July 2023

Biophysical muscle models, also known as Huxley-type models, are appropriate for simulating non-uniform and unsteady contractions. Large-scale simulations can be more challenging to use because this type of model can be computationally intensive. The method of characteristics is typically used to solve Huxley’s muscle equation, which describes the distribution of connected myosin heads to the actin-binding sites. Once this equation is solved, we can determine the generated force and the stiffness of the muscle fibers, which may then be employed in the macro-level simulations of finite element analysis. In our paper, we developed a physics-informed surrogate model that functions similarly to the original Huxley muscle model but uses a lot less computational resources in order to enable more effective use of the Huxley muscle model.
Estima de la densidad de una población de jabalí (Sus scrofa) mediante trampeo fotográfico: estudio piloto en Cataluña
Authors: Casa-Díaz Encarnación , Peris Albert , Serrano Emmanuel , Closa-Sebastià Francesc , Torrentó Josep , Miño Àngel , Casanovas Ricard , Marco Ignasi , Lavín Santiago
Published: July 2023

The wild boar (Sus scrofa L.) is an abundant mammal but difficult to watch, a fact that favours the lack of consensus about the most appropriate method to estimate their abundance. The goal of the present study is to evaluate the viability of the capture-mark-resight method using camera traps to estimate the abundance of wild boars in the Wildlife Refuge Les Refardes - La Vall, in the Natural Park of Sant Llorenç del Munt i l’Obac (NO Barcelona). After capturing and identifying 14 wild boars, 4 adults (1 male and 3 females), 2 young males and 8 piglets (5 males and 3 females), six cameras were installed and baited regularly with corn. Every week the pictures were downloaded and analyzed recording the identity, sex and age class of each individual. After five months of study (April-August 2008), with an effort of 906 days-camera, 2528 photographs of wild boars were taken. Through the estimator of Bowden implemented in the program Noremark®, we estimate a total of 23 individuals in the study area (4 wild boars/ Km2, 2.55-5.78 wild boars/Km2 IC 95%). According to these results, the capture-mark-resight method is feasible in Mediterranean environments and is a versatile technique for estimating the abundance and understanding the structure of a population of wild boars. The cameras should not be placed at capture points for the period of recapture, as these alter the behaviour of animals by decreasing their presence.
Economic evaluation of acute lymphoblastic leukemia treatment with clofarabine (Evoltra) combined with chemotherapy for children and adolscents in Poland
Authors: Szafaryn Małgorzata , Lis Joanna
Published: July 2023

Background: To evaluate the cost-effectiveness of using clofarabine (Evoltra®) in combination chemotherapy (cyclophosphamide + etoposide) vs. nelarabine and IDA-FLAG protocol (idarubicin, fludarabine, cytarabine, GCSF - Granulocyte Colony Stimulating Factor, cytarabine) for the treatment of acute lymphoblastic leukaemia among children and adolescents who have relapsed or are refractory, after receiving at least two prior standard cyclesregimens and in casewhere there areis no other options enablingtreatment option anticipated to predictresult in a long-termdurable response (as a third-line therapy, used among people qualified for patients qualifying for hematopoietic stem cell transplantation), in the Polish setting. Methods: The economic analysis was conducted on the basis of results of a systematic review. The cost analysis was carried out from the public payer (the National Health Fund) perspective in Poland, assuming that Evoltra® is financed from public funds within the chemotherapy catalogue. Direct medical costs were taken into account. Medical resources usage was determined on the basis of the results of a survey conducted in Polish centers specialized in haematology and children’s oncology. The time horizon corresponds to the patients’ life expectancy. Costs and health effects were discounted at 5% and 3.5% rate, respectively. The cost threshold for an additional quality-adjusted life year (QALY) is in line with the requirements of the Agency for Health Technology Assessment and amounts to PLN 99,543. Results: Gaining an additional life year due to the use of clofarabine instead of nelarabine and IDA-FLAG protocol is associated with the cost from the public payer perspective PLN 27,529 and 26,046 respectively within the lifetime horizon. Cost of additional quality-adjusted life year (QALY) has been estimated at PLN 32,600 and 30,336 respectively. The results of probability sensitivity analysis confirmed stability of conclusions from the basic analysis. Conclusions: Clofarabine (Evoltra®) used in combination chemotherapy for recurrent or refractory acute lymphoblastic leukaemia in children and adolescents is highly cost-effective therapeutic option in Poland compared with nelarabine and IDA-FLAG regimen.
Cost-effectiveness analysis of Human Papillomavirus (HPV) vaccination using Cervarix® as an extension to the cervical cancer prevention programme in Poland
Authors: Wepsięć Katarzyna , Gąsiorowski Marcin , Pankiewicz Oskar , Nowakowski Andrzej
Published: July 2023

Background: The aim of the study was to estimate the cost-effectiveness of addition of human papillomavirus (HPV) vaccination to the Polish cervical cancer prevention programme. Methods: A cost-utility analysis was conducted. A lifetime Markov model, adapted to Polish settings, was used to compare the costs and health outcomes of the two strategies, i.e. the existing cervical cancer prevention programme with or without universal HPV vaccination in girls at the age of 14. Results: Assuming that the whole cohort was vaccinated (100% vaccination coverage), the estimated lifetime risk of developing cervical cancer would be reduced from 0.95% to 0.23%; therefore, 1311 cases of cervical cancer and 681 deaths due to cervical cancer would be prevented in a cohort of 182,000 girls aged 14 years.If the assumed vaccination coverage was 24%, the cost of gaining an additional quality-adjusted life year (QALY) due to HPV vaccination as an extension of the cervical cancer prevention programme would be PLN 52,737.91/QALY and PLN 76,288.47/QALY from the public payer’s perspective and the common perspective of the public payer and the patient, respectively.This cost effectiveness is maintained for different parameter assumptions in the sensitivity analysis. Even with high assumed discount rates for costs and health outcomes (5% for both), the ICUR value was still lower than the cost-effectiveness threshold (PLN 105,801 per QALY). Conclusion: Addition of HPV vaccination to the cervical cancer prevention programme in Poland is a highly cost-effective intervention.
Verification of Healthcare Needs by the Use of National Health Fund Data - Mental and Behavioural Disorders
Authors: Michalak Jacek , Fałek Artur , Brzozowska Melania , Marczak Michał
Published: July 2023

Background: The ways of gaining the information on healthcare should be verified as the discrepancies between different sources may lead to serious mistakes. Unfortunately, there are few reports on the methodology on healthcare needs assessment especially when mental and behavioural disorders are considered. Methods: The whole-nation statistical data from the Central Statistical Office (CSO) were compared to the whole-nation information on the reimbursed psychotropic medicines from the National Health Found. The most important mental health problems, and the spatial (regional) distribution of mental disorders in Poland were analysed. Results: In 2011 the total number of outpatients registered in psychiatric facilities was 1 404 148 (CSO), and NHF reimbursed psychotropic drugs for 7 870 481 people. The ”neurotic disorders” and “affective disorders” were the most frequent mental problems according to CSO but NHF recognized “alcohol dependence syndrome” and “other neurotic disorders” as the most frequent mental health problems in Poland. The mental health needs in general population according to NHF data were 5,61 times higher than the needs for psychiatric care in outpatient facilities according to CSO. In some regions those differences were higher: up to 8 – 13 times. Conclusion: The comparison of data from CSO and NHF revealed the important spatial differences in healthcare inequalities, scale of double-registration of patients and overconsumption of medicines together with underestimation of healthcare needs. Also other information e.g. on patients’ non-compliance in alcohol dependence syndrome can be obtained in this way.
Cost effectiveness of the fixed combination of indacaterol/glycopyrronium versus salmeterol/ fluticasone and tiotropium in the management of patients with COPD in Greece
Authors: Geitona Mary , Kalogerolpoulou Maria , Mitsiki Eirini , Steiropoulos Paschalis
Published: July 2023

Background: This study aimed at estimating the cost-effectiveness of the fixed-dose combination indacaterol/glycopyrronium (IND/GLY) 85/43μg versus salmeterol/ fluticasone 50/500μg (SFC) and tiotropium 18μg (TIO) in the management of patients with chronic obstructive pulmonary disease (COPD) in Greece. Methods: A microsimulation model was developed in MS Excel. Effectiveness and utility data were obtained from the international literature and mortality data from the WHO database. Distribution of patients by severity stage of airflow limitation, maintenance costs and costs associated with severe/ non-severe exacerbations were taken from published Greek studies. Unit costs were taken from officially published sources (Price Bulletin, reimbursement list, diagnosis-related groups). The study perspective was that of the Social Insurance Fund; costs and outcomes were discounted at 3.5%, and the outcomes are reported over time horizons of one, three, five and 10 years and over a lifetime. Deterministic and probabilistic sensitivity analyses were conducted to test robustness of model results. Results: Treatment of COPD with IND/GLY is associated with increased efficacy both versus SFC (additional life years -LYs: 0.19; additional quality adjusted life-years -QALYs: 0.13) and TIO (additional LYs: 0.22; QALYs: 0.16). Although IND/GLY has a higher pharmaceutical cost (additional €2,626 vs. SFC; additional €2,679 vs. TIO), all other cost components (maintenance costs, severe and non-severe exacerbation costs) are reduced, resulting in a reduction of total costs by €5,204 compared with SCF and €7,126 compared with TIO. Conclusions: IND/GLY was found to be a dominant treatment strategy compared to SFC and TIO for the management of patients with COPD in Greece, which could lead to savings for the healthcare system.
RWE in Europe – An Analysis
Authors: Gill Jennifer
Published: July 2023

Background – This paper outlines findings from four roundtable discussions involving a number of stakeholders. They aimed to improve understanding of the use of real world evidence (RWE) across Europe. They focused on the development of a three-year roadmap for the increased incorporation of RWE, increasingly recognized as a valuable source of information for market access and reimbursement, in decision-making. Methods – The meetings involved participants from 12 European countries. Participants had significant knowledge of specialist disease areas and commissioning of care and prior experience in the field of RWE. All four meetings involved plenary sessions with opportunity for discussion and feedback from participants. Specific topics of interest included the role of RWE in licensing, commissioning, clinical and patients and outcomes in chronic disease, oncology and rare diseases. Results – We garnered significant insight into the current and future use of RWE across Europe, developing a three-year roadmap of initiatives for the enhanced use of RWE in decision-making. Four initiatives were seen to be the most important at this stage: actively engaging in early dialogue with payers on RWE needs; a consensus exercise on RWD/RWE in clinical decisions; developing a definition of Patient Reported and Patient Relevant Outcomes (PRO); and developing a model approach for the collection of PRO. Conclusions – The roundtable discussions generated a wealth of information around the current and future value of RWE across Europe. Significant work is required in the areas of data generation, interpretation and use to make its inclusion in commissioning and licensing based decision-making more mainstream.
Major Cardiovascular Consequences of Familial Hypercholesterolemia in Poland from the Economic Perspective
Authors: Kamińska Ewa , Wójcik Alicja , Młyńczak Katarzyna , Lis Joanna , Dąbrowska Marta , Wójtowicz Beata , Smolarska Anna , Gora Anna , Niewada Maciej , Golicki Dominik
Published: July 2023

Background. Familial hypercholesterolemia (FH) is a genetic disease characterised by high LDL-C level with other lipid fractions levels typically correct. The disease involves the accelerated development of arteriosclerosis and vascular complications, mainly coronary disease. Patients with FH have an increased risk of the acute coronary syndrome (ACS), ischemic stroke (IS) and peripheral artery disease (PAD). Aims. This publication aims to discuss epidemiology and costs associated with three major vascular complications of FH: ACS (including myocardial infarction, MI), IS and PAD. In case of lack of specific data for FH subpopulation, more general data will be discussed. Results. Meta-analysis of six Polish population studies indicated that heterozygous FH morbidity in Poland is approximately 404/100,000 people what corresponds with approximately 150,000 patients. Each year 123 thousand ACS are reported in Poland of what approximately 62% is a MI. In European population FH is diagnosed in approximately 8.3% patients with ACS (in Polish subpopulation – approximately 11.4%). Total hospitalization costs due to ACS among patients with FH in 2016 equaled PLN 108-148 million, of what hospitalization cost due to MI was approximately PLN 67-91 million. Indirect medical costs during first 36 months after MI in patients with FH may be estimated for PLN 128-175 million and indirect costs of MI in patients with FH for PLN 257-684 million. Conclusions. Early screening for familial hypercholesterolemia and efficient hypolipemic treatment are a chance for significant reduction of incidence of discussed vascular complications and their costs within the healthcare system. We were not able to identify any specific cost data for FH subpopulations of IS and PAD patients.
Cost-effectiveness analysis of methods of diagnosis of tb infection in russian regions by use of recombinant tb allergen in children and adolescents.
Authors: Hołownia-Voloskova Malwina , Bashlakova Ekaterina , Ermolaeva Tatyana , Davydovskaya Maria , Evdoshenko Evgeniy
Published: July 2023

Background. Russia is among the countries with a high burden of TB. A new diagnostic method for TB has been developed, called ‘recombinant tuberculosis allergen’ or RTA (Diaskintest®), which has a similar cost and method of administration to the Mantoux test, but the principle of action, sensitivity and specificity are similar to IGRA technology. Despite the improvements of RTA, TB experts continue to use the Mantoux test. The aim of this study was to determine the most cost-effective medical technology for diagnosing tuberculosis infection in the Russian Federation, basing on calculation of ICER. Methods. The study was based on 3 models simulating the diagnosis of TB in Russia: 1-Mantoux test and further diagnostics methods (based on screening in 2008 in 1,302,490 Moscow children and adolescents); 2-Mantoux test with subsequent use of RTA in case of a positive Mantoux test, combined with further diagnostics methods (based on screening in 2013 in 1,420,100 Moscow children and adolescents); 3-RTA alone and further diagnostics methods (data based on screening conducted in 2015 in 108,729 Penza region children and adolescents 8-17 y.o.). Results. Method effectiveness (percentage of active TB infection among screened individuals), was 0.006%, 0.012% and 0.019% for models 1, 2 and 3, respectively. Cost-effectiveness ratios were 41861.67, 18401.67 and 10512.12 for models 1, 2 and 3, respectively. Conclusions. RTA is the most cost-effective tuberculosis screening method in children and adolescents, superior to both the stand-alone Mantoux test or the Mantoux test followed by RTA.
Patients' opinions on metoprolol, as expressed on the Internet - an exploratory, qualitative study
Authors: Świeczkowski Damian , Cwalina Natalia , Jaguszewski Miłosz
Published: July 2023

Background Use of the Internet in health communication provides an opportunity for more effective discussions, consequently Internet forums are potential sources of drug-related information for the patients. However, we must consider the possibility of misinformation that exists in the virtual environment. We explore patients’ perceptions and attitudes towards metoprolol as stated on the Internet. We equated patients’ opinions published on the Internet with written information available in Poland for patients and physicians. Methods This is an exploratory, qualitative study. Data was analyzed thematically. Themes were identified inductively from the data as described by experts in the field of qualitative studies. To obtain data from a variety of individuals, they were collected from three websites that were publicly available and patient-directed. Results Five themes were identified: weight gain, impact on sleep and mood, interactions between alcohol and drugs, using metoprolol during gestation, and a connection between sexual dysfunction and pharmacotherapy. Patients described their concerns as associated directly with the pharmacotherapy. Patients declared that their physician had no time to explain drug-related problems during the examination. In the Consumer Medicine Information (leaflets), all the information that could prove beneficial for solving a patient's confusion, misinterpretations and concerns, can be found. Conclusions Internet forums are not reliable sources of medicine-related information. Most opinions included in this study presented as poor quality and should be considered potentially risky for the patients and might be unsafe in the field of public health issues. Further study should be based on quantitative methods or triangulation concept.
Secondary immunodeficiencies – do we need systemic solutions?
Authors: Jahnz-Różyk Karina , Roliński Jacek , Siedlar Maciej , Jędrzejczak Wiesław , Sydor Wojciech , Tomaszewska Agnieszka , Więsik-Szewczyk Ewa
Published: July 2023

Secondary immunodeficiencies are becoming more common as they can develop in the course of numerous diseases and result from a variety of therapeutic procedures including allogeneic hematopoietic stem cell transplantation, solid organ transplantations and biological therapies, especially B cell depleting therapies, which have been recently used with increasing frequency. Although the problem is very important, consensus guidelines on the indications, regimens and monitoring of the immunoglobulin replacement therapy in this group patients are lacking. Therefore, it is necessary to perform epidemiological assessment of the frequency of secondary immunodeficiency disorders in Poland and to make the best use of the experience gained in other countries in the field of the immunoglobulin replacement therapy including eligibility criteria, dosage regimens and duration of treatment and to combine them with cost-effectiveness analysis. Provision patients with the opportunity of home treatment with subcutaneous immunoglobulin, which has proven highly beneficial in patients with primary immunodeficiency disorders, seems to be of key importance.
The Polish Expert Group Position Statement on the Safety of Biological Treatments with Monoclonal Antibodies and Fusion Proteins: An Update
Authors: Jahnz-Różyk Karina , Brzosko Marek , Lech-Marańda Ewa , Narbutt Joanna , Owczarek Witold , Rękas Marek , Styczyński Jan , Różanowski Paweł , Zagórowicz Edyta , Zyśk Rafał , Więsik-Szewczyk Ewa
Published: July 2023

﻿Objective: The introduction of biological drugs, including monoclonal antibodies and fusion proteins, into therapeutics is among the greatest achievements of modern medicine. These agents have been successfully used in oncology, haematology, rheumatology, gastroenterology, ophthalmology, dermatology, and allergology. Herein, we present a consensus of expert opinion regarding biologics use as an update to the Expert Group Position Statement published in 2014. Considering the rapid development within this field and the evidence accumulated in the last few years with the use of innovative biologics and biosimilars, an update has become necessary. The importance of real-world evidence from observational studies and medical registries and the way it complements data from randomised studies will be highlighted. Therefore, the expert opinion regarding switching between bio-originator and biosimilar therapeutics, immunogenicity, pharmacovigilance, and the costs of biological treatments is constantly in flux. Methods: An expert panel of national consultants, members of the coordination teams of Polish drug programs, and specialists with expertise in biological treatments participated in this study in order to establish a consensus on the most critical aspects of biological treatment in Poland. A modified Delphi method was performed to achieve a consensus on relevant statements, which was met if at least 80% of experts agreed or disagreed with the discussed statement. Results: The current expert position on the use of biosimilars in everyday practice was thoroughly investigated. For nine of the presented statements, panellists agreed that the expected cost savings due to biosimilars introduction, safety of extrapolation of indications, single switching bio-originator and biosimilar. Moreover, the overall access to biological treatment in Poland was explored. Conclusion: The present analysis will serve as a guide to physicians that prescribe biological treatments to aid them in the critical analysis on the use of biosimilars and will further support treatment decisions and patient education on the subject.
Cost-utility analysis of tafamidis for the treatment of adult patients with transthyretin familial amyloid polyneuropathy in Poland
Authors: Borowiack Ewa , Marzec Magdalena , Jarosz Joanna , Snarska Katarzyna , Konopka-Pliszka Małgorzata
Published: July 2023

Background: The aim of this publication was to evaluate the cost-effectiveness of oral tafamidis (TAF) versus placebo (both used with standard of care, SOC) for the treatment of transthyretin amyloidosis in adult patients with stage 1 symptomatic polyneuropathy in order to delay peripheral neurologic impairment. Methods: The Markov model constructed in TreeAge Pro with 50-year time horizon was used in the cost-utility analysis (CUA). Quality adjusted life years (QALY) were used as the measure of effectiveness. CUA was conducted from the perspective of the public payer for health services (Polish National Health Fund, PNHF) and from the patient’s and PNHF’s perspective. For both perspectives only direct medical costs were included. Utility weights were obtained from the literature. Results: The cost of gaining an additional QALY by replacing SOC with TAF+SOC is equal 1,012,424 PLN /1,012,631 PLN (235,098 €/ 235,146 €) from PNHF/PNHF+patient’s perspective. Conclusion: Introduction of tafamidis to the regimen occurred to be more effective and more expensive than standard of care alone. The use of TAF resulted in almost 3 additional QALY compared with SOC, in lifetime horizon.
Cost per Responder Analysis of Biologics in Moderate-to-severe Plaque Psoriasis in Indian Healthcare Setting
Authors: Gokhale Sameer , Arora Sandeep , Kawatra Pallavi
Published: July 2023

Background: Moderate-to-severe plaque psoriasis (PsO) affects >8 million Indians and has a detrimental effect on quality of life (QoL). Effective skin clearance can be one of the important factors for improving patient’s QoL. Newer biologics offer significant levels of skin clearance eventually improving QoL. However high cost of originator biologics is an impediment and poses a challenge for healthcare stakeholder to choose more efficacious and cost-effective biologic among the available options. Aims: To estimate the annual cost per responder (CPR) in PsO patients in India based on Psoriasis Area Severity Index (PASI)-75/90 for 52-weeks of treatment and estimate the number needed to treat (NNT). Methods: CPR has been developed to compare direct medical costs. The tool enables the user to input epidemiology numbers, level of drug usage and allows user to decide the biologic to choose to offer better health outcomes. Efficacy for biologics under evaluation were reported from the network meta-analysis and measured as proportion of patients achieving PASI-75/90 at week-52. NNT to obtain one patient with a PASI-75/90 response was henceforth calculated. Results: The tool demonstrates CPR and NNT results dynamically with user provided inputs. Additional number of responders who could potentially be treated with the biologic under consideration with the annual cost-savings generated were also presented. This will help users to assess comparative effectiveness of a biologic intervention by combining clinical and economic dimensions. Conclusion: This CPR tool supports evidence-based decision making for improved health outcomes in the Indian healthcare setting.
Dynamic regulation of inter-organelle communication by ubiquitylation controls skeletal muscle development and disease onset
Authors: Mansur Arian , Joseph Remi , Kim Euri S , Jean-Beltran Pierre M , Udeshi Namrata D , Pearce Cadence , Jiang Hanjie , Iwase Reina , Milev Miroslav P , Almousa Hashem A , McNamara Elyshia , Widrick Jeffrey , Perez Claudio , Ravenscroft Gianina , Sacher Michael , Cole Philip A , Carr Steven A , Gupta Vandana A
Published: July 2023

Ubiquitin-proteasome system (UPS) dysfunction is associated with the pathology of a wide range of human diseases, including myopathies and muscular atrophy. However, the mechanistic understanding of specific components of the regulation of protein turnover during development and disease progression in skeletal muscle is unclear. Mutations in KLHL40, an E3 ubiquitin ligase cullin3 (CUL3) substrate-specific adapter protein, result in severe congenital nemaline myopathy, but the events that initiate the pathology and the mechanism through which it becomes pervasive remain poorly understood. To characterize the KLHL40-regulated ubiquitin-modified proteome during skeletal muscle development and disease onset, we used global, quantitative mass spectrometry-based ubiquitylome and global proteome analyses of klhl40a mutant zebrafish during disease progression. Global proteomics during skeletal muscle development revealed extensive remodeling of functional modules linked with sarcomere formation, energy, biosynthetic metabolic processes, and vesicle trafficking. Combined analysis of klh40 mutant muscle proteome and ubiquitylome identified thin filament proteins, metabolic enzymes, and ER-Golgi vesicle trafficking pathway proteins regulated by ubiquitylation during muscle development. Our studies identified a role for KLHL40 as a regulator of ER-Golgi anterograde trafficking through ubiquitin-mediated protein degradation of secretion-associated Ras-related GTPase1a (Sar1a). In KLHL40-deficient muscle, defects in ER exit site vesicle formation and downstream transport of extracellular cargo proteins result in structural and functional abnormalities. Our work reveals that the muscle proteome is dynamically fine-tuned by ubiquitylation to regulate skeletal muscle development and uncovers new disease mechanisms for therapeutic development in patients.
How enhancers regulate wavelike gene expression patterns
Authors: Mau Christine , Rudolf Heike , Strobl Frederic , Schmid Benjamin , Regensburger Timo , Palmisano Ralf , Stelzer Ernst HK , Taher Leila , El-Sherif Ezzat
Published: July 2023

A key problem in development is to understand how genes turn on or off at the right place and right time during embryogenesis. Such decisions are made by non-coding sequences called ‘enhancers.’ Much of our models of how enhancers work rely on the assumption that genes are activated de novo as stable domains across embryonic tissues. Such a view has been strengthened by the intensive landmark studies of the early patterning of the anterior-posterior (AP) axis of the Drosophila embryo, where indeed gene expression domains seem to arise more or less stably. However, careful analysis of gene expression patterns in other model systems (including the AP patterning in vertebrates and short-germ insects like the beetle Tribolium castaneum) painted a different, very dynamic view of gene regulation, where genes are oftentimes expressed in a wavelike fashion. How such gene expression waves are mediated at the enhancer level is so far unclear. Here, we establish the AP patterning of the short-germ beetle Tribolium as a model system to study dynamic and temporal pattern formation at the enhancer level. To that end, we established an enhancer prediction system in Tribolium based on time- and tissue-specific ATAC-seq and an enhancer live reporter system based on MS2 tagging. Using this experimental framework, we discovered several Tribolium enhancers, and assessed the spatiotemporal activities of some of them in live embryos. We found our data consistent with a model in which the timing of gene expression during embryonic pattern formation is mediated by a balancing act between enhancers that induce rapid changes in gene expression patterns (that we call ‘dynamic enhancers’) and enhancers that stabilize gene expression patterns (that we call ‘static enhancers’). However, more data is needed for a strong support for this or any other alternative models.
SNORD90 induces glutamatergic signaling following treatment with monoaminergic antidepressants
Authors: Lin Rixing , Kos Aron , Lopez Juan Pablo , Dine Julien , Fiori Laura M , Yang Jennie , Ben-Efraim Yair , Aouabed Zahia , Ibrahim Pascal , Mitsuhashi Haruka , Wong Tak Pan , Ibrahim El Cherif , Belzung Catherine , Blier Pierre , Farzan Faranak , Frey Benicio N , Lam Raymond W , Milev Roumen , Muller Daniel J , Parikh Sagar V , Soares Claudio , Uher Rudolf , Nagy Corina , Mechawar Naguib , Foster Jane A , Kennedy Sidney H , Chen Alon , Turecki Gustavo
Published: July 2023

Pharmacotherapies for the treatment of major depressive disorder were serendipitously discovered almost seven decades ago. From this discovery, scientists pinpointed the monoaminergic system as the primary target associated with symptom alleviation. As a result, most antidepressants have been engineered to act on the monoaminergic system more selectively, primarily on serotonin, in an effort to increase treatment response and reduce unfavorable side effects. However, slow and inconsistent clinical responses continue to be observed with these available treatments. Recent findings point to the glutamatergic system as a target for rapid acting antidepressants. Investigating different cohorts of depressed individuals treated with serotonergic and other monoaminergic antidepressants, we found that the expression of a small nucleolar RNA, SNORD90, was elevated following treatment response. When we increased Snord90 levels in the mouse anterior cingulate cortex (ACC), a brain region regulating mood responses, we observed antidepressive-like behaviors. We identified neuregulin 3 (NRG3) as one of the targets of SNORD90, which we show is regulated through the accumulation of N6-methyladenosine modifications leading to YTHDF2-mediated RNA decay. We further demonstrate that a decrease in NRG3 expression resulted in increased glutamatergic release in the mouse ACC. These findings support a molecular link between monoaminergic antidepressant treatment and glutamatergic neurotransmission.
Spatial transcriptomics of meningeal inflammation reveals inflammatory gene signatures in adjacent brain parenchyma
Authors: Gadani Sachin P , Singh Saumitra , Kim Sophia , Hu Jingwen , Smith Matthew D , Calabresi Peter A , Bhargava Pavan
Published: July 2023

While modern high efficacy disease modifying therapies have revolutionized the treatment of relapsing-remitting multiple sclerosis, they are less effective at controlling progressive forms of the disease. Meningeal inflammation is a recognized risk factor for cortical gray matter pathology which can result in disabling symptoms such as cognitive impairment and depression, but the mechanisms linking meningeal inflammation and gray matter pathology remain unclear. Here, we performed magnetic resonance imaging (MRI)-guided spatial transcriptomics in a mouse model of autoimmune meningeal inflammation to characterize the transcriptional signature in areas of meningeal inflammation and the underlying brain parenchyma. We found broadly increased activity of inflammatory signaling pathways at sites of meningeal inflammation, but only a subset of these pathways active in the adjacent brain parenchyma. Subclustering of regions adjacent to meningeal inflammation revealed the subset of immune programs induced in brain parenchyma, notably complement signaling and antigen processing/presentation. Trajectory gene and gene set modeling analysis confirmed variable penetration of immune signatures originating from meningeal inflammation into the adjacent brain tissue. This work contributes a valuable data resource to the field, provides the first detailed spatial transcriptomic characterization in a model of meningeal inflammation, and highlights several candidate pathways in the pathogenesis of gray matter pathology.
Efficacy of Prophylactic Norepinephrine and Phenylephrine Infusions against Spinal Hypotension during Lower Segment Caesarean Section- A Randomised Clinical Study
Authors: Priya Pachha , Devaraj IC , Shetty Nisha S , D Srinivasalu D Srinivasalu , Kiranchand N , Bhaskar S Bala
Published: July 2023

Introduction: Hypotension after Subarachnoid Block (SAB) can affect mother and foetus and can be prevented by prophylactic use of vasopressors. Phenylephrine (PE) has been a popular and effective drug as prophylaxis against hypotension. Norepinephrine (NE) is recently tried for this purpose. Aim: To compare PE infusion with NE infusion prophylactically against SAB induced hypotension during Lower Segment Cesarean Section (LSCS). Materials and Methods: This randomised clinical study was conducted in the Department of Anaesthesiology at a Tertiary Care Hospital, Ballari, Karnataka, India. The duration of the study was 12 months, from December 2018 to November 2019. A total of 156 primigravida and multigravida with singleton term pregnancy, posted for caesarean section under SAB received prophylactic infusions of either NE 5 μg/minute (group NE) or PE 50 μg/minute (group PE) immediately after SAB till end of the surgery. The primary outcome of the study was to assess the incidence of hypotension. The secondary outcomes included incidence of nausea, vomiting, hypertension, tachycardia, bradycardia and the neonatal outcomes. Related categorical and numerical variables were subjected to suitable statistical tests and analysed using Statistical Package for Social Sciences (SPSS) version 20.0. Results: The mean age of the study participants of group NE was 24.47±2.52 years and group PE was 23.91±2.63 years, respectively. The age, parity and surgical duration was comparable between the groups. The incidence of hypotension was 17.9% in group NE and 26.8% in group PE (p-value=0.182). No significant differences in total doses of vasopressors used were noted. The incidence of bradycardia in group NE was 3.8% and 21.8% in the group PE (p=0.053). No adverse events or neonatal outcomes were observed. Conclusion: The incidence of hypotension and the total dose of vasopressors administered were similar in the two groups receiving prophylactic infusion doses (NE or PE). Incidence of bradycardia was greater in the parturients receiving PE infusion.