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ABSTRACTDendritic cells (DCs) play a key role in the induction of the adaptive immune response. They capture antigens in peripheral tissues and prime naïve T lymphocytes, triggering the adaptive immune response. In the course of inflammatory processes DCs face stressful conditions including hypoxia, low pH and high concentrations of reactive oxygen species (ROS), among others. How DCs survive under these adverse conditions remain poorly understood. Clusterin is a protein highly expressed by tumors and usually associated with bad prognosis. It promotes cancer cell survival by different mechanisms such as apoptosis inhibition and promotion of autophagy. Here, we show that, upon maturation, human monocyte-derived DCs (MoDCs) up-regulate clusterin expression. Clusterin protects MoDCs from ROS-mediated toxicity, enhancing DC survival and promoting their ability to induce T cell activation. In line with these results, we found that clusterin is expressed by a population of mature LAMP3+ DCs, called mregDCs, but not by immature DCs in human cancer. The expression of clusterin by intratumoral DCs was shown to be associated with a transcriptomic profile indicative of cellular response to stress. These results uncover an important role for clusterin in DC physiology.

Tujuan dari pengabdian kepada masyarakat ini adalah untuk meningkatkan kompetensi dan keterampilan siswa SMAN 6 Malang khususnya dalam bidang kosmetika, guna meningkatkan kemampuan dan kesiapannya dalam mengaplikasikan kosmetika khususnya lulur aromatik dari kulit lemon yang kaya akan antioksidan. Ekstrak kulit jeruk nipis merupakan tanaman yang mempunyai manfaat sebagai antioksidan alami karena mengandung vitamin C, asam sitrat, minyak atsiri, bio-flavonoid, polifenol, kumarin, flavonoid, dan minyak atsiri pada kulitnya seperti limonene (±70%), α- terpinen, α-pinene, β-pinene, serta kumarin, dan polifenol. Metode pelaksanaan dengan tahapan perencanaan, pelaksanaan (observasi, diskusi, demonstrasi, dan penerapan praktis) dan evaluasi, dilaksanakan pengabdian masyarakat. Hasil pengabdian kepada masyarakat memberikan hasil positif dari rata-rata sampel sebanyak 26 orang yaitu skor 89 dengan predikat baik dari hasil pengolahan data. Kesimpulan pengabdian masyarakat dengan adanya program pengabdian masyarakat dapat membantu siswa SMAN 6 Malang dalam menciptakan wirausaha muda di bidang kosmetika seperti lulur aromatik dari kulit lemon dengan memberikan inovasi yang aman, mudah, dan mengembangkan bahan lokal di Kota Malang.

Abstract Background In rheumatoid arthritis (RA), the activation of T and B cell clones specific for self-antigens leads to the chronic inflammation of the synovium. Here, we perform an in-depth quantitative analysis of the seven chains that comprise the adaptive immune receptor repertoire (AIRR) in RA. Results In comparison to controls, we show that RA patients have multiple and strong differences in the B cell receptor repertoire including reduced diversity as well as altered isotype, chain, and segment frequencies. We demonstrate that therapeutic tumor necrosis factor inhibition partially restores this alteration but find a profound difference in the underlying biochemical reactivities between responders and non-responders. Combining the AIRR with HLA typing, we identify the specific T cell receptor repertoire associated with disease risk variants. Integrating these features, we further develop a molecular classifier that shows the utility of the AIRR as a diagnostic tool. Conclusions Simultaneous sequencing of the seven chains of the human AIRR reveals novel features associated with the disease and clinically relevant phenotypes, including response to therapy. These findings show the unique potential of AIRR to address precision medicine in immune-related diseases.

Abstract: Writing this article aims to find out how the extracurricular management process starts from planning, organizing, implementing, and supervising as a vehicle for educating the character of students at MI Manarul Islam and MI Khadijah Malang City. This article uses a qualitative approach with a multi-site study type of research. Data collection techniques through in-depth interviews, observation, and documentation. The informants in this study were school principals, student assistants, extracurricular coordinators, and extracurricular coaches. The results of this study indicate that the extracurricular management process in Madrasah Ibtidaiyah supports the development of the character of students, namely cooperation, religion, tolerance, mutual assistance, integrity, respect for differences, sportsmanship, maintaining cleanliness, training leadership, discipline, independence, self-confidence, responsibility, obedience , never give up, work hard, concentrate and focus, these characters will affect learning at school and outside of school. Keywords: management; extracurricular; student character Abstrak: Penulisan artikel ini bertujuan untuk mengetahui bagaimana proses manajemen ekstrakurikuler mulai dari perencanaan, pengorganisasian, pelaksanaan, dan pengawasan sebagai wahana mendidik karakter peserta didik di MI Manarul Islam dan MI khadijah Kota Malang. Artikel ini menggunakan pendekatan kualitatif dengan jenis penelitian studi multi situs. Teknik pengumpulan data melalui wawancara mendalam, observasi, dan dokumentasi. Informan dalam penelitian ini yaitu kepala sekolah, waka kesiswaan, koordinator ekstrakurikuler, dan pembina ekstrakurikuler. Hasil penelitian ini menunjukkan bahwa proses manajemen ekstrakurikuler di Madrasah Ibtidaiyah menunjang pengembangan karakter peserta didik yaitu bekerja sama, religius, bertoleransi, saling membantu, integritas, menghormati perbedaan, sportifitas, menjaga kebersihan, melatih kepemimpinan, disiplin, mandiri, percaya diri, bertanggungjawab, ketaatan, pantang menyerah, bekerja keras, berkonsentrasi dan fokus, karakter tersebut akan berpengaruh terhadap pembelajaran di sekolah maupun di luar sekolah. Kata kunci: manajemen; ekstrakurikuler; karakter peserta didik

Objectives To investigate pregnancy outcomes in women with autoimmune rheumatic diseases (ARD) in the Italian prospective cohort study P-RHEUM.it.Methods Pregnant women with different ARD were enrolled for up to 20 gestational weeks in 29 Rheumatology Centres for 5 years (2018–2023). Maternal and infant information were collected in a web-based database.Results We analysed 866 pregnancies in 851 patients (systemic lupus erythematosus was the most represented disease, 19.6%). Maternal disease flares were observed in 135 (15.6%) pregnancies. 53 (6.1%) pregnancies were induced by assisted reproduction techniques, 61 (7%) ended in miscarriage and 11 (1.3%) underwent elective termination. Obstetrical complications occurred in 261 (30.1%) pregnancies, including 2.3% pre-eclampsia. Two cases of congenital heart block were observed out of 157 pregnancies (1.3%) with anti-Ro/SSA. Regarding treatments, 244 (28.2%) pregnancies were treated with glucocorticoids, 388 (44.8%) with hydroxychloroquine, 85 (9.8%) with conventional synthetic disease-modifying anti-rheumatic drugs and 122 (14.1%) with biological disease-modifying anti-rheumatic drugs. Live births were 794 (91.7%), mostly at term (84.9%); four perinatal deaths (0.5%) occurred. Among 790 newborns, 31 (3.9%) were small-for-gestational-age and 169 (21.4%) had perinatal complications. Exclusive maternal breast feeding was received by 404 (46.7%) neonates. The Edinburgh Postnatal Depression Scale was compiled by 414 women (52.4%); 89 (21.5%) scored positive for emotional distress.Conclusions Multiple factors including preconception counselling and treat-to-target with pregnancy-compatible medications may have contributed to mitigate disease-related risk factors, yielding limited disease flares, good pregnancy outcomes and frequency of complications which were similar to the Italian general obstetric population. Disease-specific issues need to be further addressed to plan preventative measures.

Objective To assess the predictive value of four cardiovascular (CV) risk algorithms for identifying high-risk psoriatic arthritis (PsA) patients.Methods Evaluation of patients with PsA enrolled in the Spanish prospective project CARdiovascular in RheuMAtology. Baseline data of 669 PsA patients with no history of CV events at the baseline visit, who were followed in rheumatology outpatient clinics at tertiary centres for 7.5 years, were retrospectively analysed to test the performance of the Systematic Coronary Risk Assessment (SCORE), the modified version (mSCORE) European Alliance of Rheumatology Associations (EULAR) 2015/2016, the SCORE2 algorithm (the updated and improved version of SCORE) and the QRESEARCH risk estimator version 3 (QRISK3).Results Over 4790 years of follow-up, there were 34 CV events, resulting in a linearised rate of 7.10 per 1000 person-years (95% CI 4.92 to 9.92). The four CV risk scales showed strong correlations and all showed significant associations with CV events (p

Recently, we described a phenomenon whereby apoptotic cells generate and release CrkI-containing microvesicles, which stimulate proliferation in surrounding cells upon contact to compensate for their own demise. We termed these microvesicles ACPSVs for Apoptotic Compensatory Proliferation Signaling microvesicles. As immune cells and a majority of current cancer therapeutics destroy tumor cells primarily by apoptosis, we conducted a small pilot study to assess the possibility that ACPSVs may also be generated in squamous cell carcinomas. We first evaluated a primary and a metastatic squamous cell carcinoma cancer cell lines for their ability to produce ACPSVs under normal and apoptotic conditions. We next conducted a pilot study to assess the occurrence of ACPSVs in solid tumors extracted from 20 cancer patients with squamous cell carcinomas. Both cancer cell lines produced copious amounts of ACPSVs under apoptotic conditions. Interestingly, the metastatic squamous cell carcinoma cancer cell line also produced high levels of ACPSVs under healthy condition, suggesting that the ability to generate ACPSVs may be hijacked by these cells. Importantly, ACPSVs were also abundant in the solid tumors of all squamous cell carcinoma cancer patients. Detection of ACPSVs in cancer has potentially important ramifications in tumor biology and cancer therapeutics which warrants further investigation.

A great number of educational institutions worldwide have had their activities partially or fully interrupted following the outbreak of the COVID-19 pandemic. Consequently, universities have had to take the necessary steps in order to adapt their teaching, including laboratory workshops, to a fully online or mixed mode of delivery while maintaining their academic standards and providing a high-quality student experience. This transition has required, among other efforts, adequate investments in tools, accessibility, content development, and competences as well as appropriate training for both the teaching and administrative staff. In such a complex scenario, Virtual Reality Laboratories (VRLabs), which in the past already proved themselves to be efficient tools supporting the traditional practical activities, could well represent a valid alternative in the hybrid didactic mode of the contemporary educational landscape, rethinking the educational proposal in light of the indications coming from the scientific literature in the pedagogical field. In this context, the present work carries out a critical review of the existent virtual labs developed in the Engineering departments in the last ten years (2010-2020) and includes a pre-pandemic experience of a VRLab tool - StreamFlowVR - within the Hydraulics course of Basilicata University, Italy. This analysis is aimed at highlighting how ready VRLabs are to be exploited not only in emergency but also in ordinary situations, together with valorising an interdisciplinary dialogue between the pedagogical and technological viewpoints, in order to progressively foster a high-quality and evidence-based educational experience.

Urban development and increasing population impact improving the demand for non-agricultural land. Through the issuance of Law No. 41 of 2009 concerning the Protection of Sustainable Food Agricultural Land, the government has attempted to reduce the conversion rate of agricultural land by protecting paddy fields that are considered the potential for food supply. This study aims to examine the impact of the transformation of agricultural land to non-agricultural land on food security and the implementation of the of Law No. 41 of 2009. The research method used is survey and descriptive. The focus of discussion includes population growth, land change, land area, harvested area, production and food availability needs data. The data was gathered from field observations, interviews and a literature study. The results showed that the average decrease in paddy fields in the last three years was 98.87 ha. The population density in Sleman Regency is classified as high. In 2018 to 2019 the population density increased by 22.88 people km-2. In 2019 to 2020 the population density decreased by 163.35 people km-2. In 2018 to 2019 rice productivity increased by 625 tons ha-1, although harvested area and production have declined. There is no correlation between the location of paddy fields, population and rice productivity. The food security condition in Sleman Regency is generally stable, but the site of paddy fields that continues to decrease yearly must still be a concern.

This study aims to collect the information needed to find a form of teaching material that fits the needs of students and the demands of a new 21st-century skill-based curriculum in writing courses at the basic secondary level (Sakubun II). The research method used is R&D with a mixed approach. These qualitative and quantitative approaches aim to describe the needs of students, lecturers, and study programs for writing teaching materials following the 21st-century curriculum. Data collection techniques were carried out in three ways: reviewing documents, questionnaires, and observation. The results showed that the Japanese Language Education Study Program FBS UNJ needed teaching materials focused on achieving writing skills and could also motivate students to have ideas and be creative in writing easily. Regarding the structure of teaching materials, various teaching materials are needed to encourage students to write in digital literacy discourse. From the questionnaire results, three needs were found at the top level, namely the need for teaching materials that focus on critical thinking skills, creativity, and basic literacy, so the portion of activities that can accommodate these needs must be enlarged.

Abstract Based on data collected as part of the contact tracing activity of the City of Helsinki Epidemiological Operations Unit, we evaluated the efficacy and effectiveness of isolating SARS-CoV-2 cases and quarantining their exposed contacts during a mildly growing phase of the COVID-19 epidemic in Finland in autumn 2020. Based on the observed symptom-to-symptom intervals in 1016 pairs of primary and secondary cases, we estimated that without case isolation or quarantine 40 $$\%$$ % (90 $$\%$$ % credible interval, CI 25–59) of transmission would have occurred on the day of or after symptom onset. One third of SARS-CoV-2 cases (N = 1521) had initially been quarantined, with a self-reported time until isolation (quarantine) of 0.8 days before symptom onset. This delay translates into an efficacy of 50 $$\%$$ % (90 $$\%$$ % CI 40–63) of averting secondary infections per quarantined case. Due to later isolation (mean 2.6 days after symptoms), the efficacy was smaller (24 $$\%$$ % ; 90 $$\%$$ % CI 12–41) in those two third of the cases (N = 3101) whose isolation was prompted by their symptoms, i.e. without being previously quarantined. At the population level, we evaluated the effectiveness of case isolation and quarantine on the growth rate of the COVID-19 epidemic in the autumn of 2020. Under a wide range of underlying assumptions, the rate would have been at least 2 times higher without case isolation and quarantine. The numbers needed to isolate or quarantine to prevent one secondary case were 2 and 20, respectively.