B cell immune profiles in dysbiotic vermiform appendixes of pancreatic cancer patients

Pancreatic ductal adenocarcinoma (PDAC) remains one of the deadliest solid tumors and is resistant to immunotherapy. B cells play an essential role in PDAC progression and immune responses, both locally and systemically. Moreover, increasing evidence suggests that microbial compositions inside the tumor, as well as in the oral cavity and the gut, are important factors in shaping the PDAC immune landscape. However, the gut-associated lymphoid tissue (GALT) has not previously been explored in PDAC patients. In this study, we analyzed healthy vermiform appendix (VA) from 20 patients with PDAC and 32 patients with colon diseases by gene expression immune profiling, flow cytometry analysis, and microbiome sequencing. We show that the VA GALT of PDAC patients exhibits markers of increased inflammation and cytotoxic cell activity. In contrast, B cell function is decreased in PDAC VA GALT based on gene expression profiling; B cells express significantly fewer MHC class II surface receptors, whereas plasma cells express the immune checkpoint molecule HLA-G. Additionally, the vermiform appendix microbiome of PDAC patients is enriched with Klebsiella pneumoniae, Bifidobacterium animalis, and Adlercreutzia equolifaciens, while certain commensals are depleted. Our findings may suggest impaired B cell function within the GALT of PDAC patients, which could potentially be linked to microbial dysbiosis. Additional investigations are imperative to validate our observations and explore these potential targets of future therapies.</p

B cell immune profiles in dysbiotic vermiform appendixes of pancreatic cancer patients

Pancreatic ductal adenocarcinoma (PDAC) remains one of the deadliest solid tumors and is resistant to immunotherapy. B cells play an essential role in PDAC progression and immune responses, both locally and systemically. Moreover, increasing evidence suggests that microbial compositions inside the tumor, as well as in the oral cavity and the gut, are important factors in shaping the PDAC immune landscape. However, the gut-associated lymphoid tissue (GALT) has not previously been explored in PDAC patients. In this study, we analyzed healthy vermiform appendix (VA) from 20 patients with PDAC and 32 patients with colon diseases by gene expression immune profiling, flow cytometry analysis, and microbiome sequencing. We show that the VA GALT of PDAC patients exhibits markers of increased inflammation and cytotoxic cell activity. In contrast, B cell function is decreased in PDAC VA GALT based on gene expression profiling; B cells express significantly fewer MHC class II surface receptors, whereas plasma cells express the immune checkpoint molecule HLA-G. Additionally, the vermiform appendix microbiome of PDAC patients is enriched with Klebsiella pneumoniae, Bifidobacterium animalis, and Adlercreutzia equolifaciens, while certain commensals are depleted. Our findings may suggest impaired B cell function within the GALT of PDAC patients, which could potentially be linked to microbial dysbiosis. Additional investigations are imperative to validate our observations and explore these potential targets of future therapies.</p

Target product profiles for neonatal care devices: systematic development and outcomes with NEST360 and UNICEF.

BACKGROUND: Medical devices are critical to providing high-quality, hospital-based newborn care, yet many of these devices are unavailable in low- and middle-income countries (LMIC) and are not designed to be suitable for these settings. Target Product Profiles (TPPs) are often utilised at an early stage in the medical device development process to enable user-defined performance characteristics for a given setting. TPPs can also be applied to assess the profile and match of existing devices for a given context. METHODS: We developed initial TPPs for 15 newborn product categories for LMIC settings. A Delphi-like process was used to develop the TPPs. Respondents completed an online survey where they scored their level of agreement with each of the proposed performance characteristics for each of the 15 devices. Characteristics with  75% agreement. Areas of disagreement were voted on by 69 participants at an in-person consensus meeting, with consensus achieved for 648 (97%) performance characteristics. Only 20 (3%) performance characteristics did not achieve consensus, most (15/20) relating to quality management systems. UNICEF published the 15 TPPs in April 2020, accompanied by a report detailing the online survey results and consensus meeting discussion, which has been viewed 7,039 times (as of January 2023). CONCLUSIONS: These 15 TPPs can inform developers and enable implementers to select neonatal care products for LMIC. Over 2,400 medical devices and diagnostics meeting these TPPs have been installed in 65 hospitals in Nigeria, Tanzania, Kenya, and Malawi through the NEST360 Alliance. Twenty-three medical devices identified and qualified by NEST360 meet nearly all performance characteristics across 11 of the 15 TPPs. Eight of the 23 qualified medical devices are available in the UNICEF Supply Catalogue. Some developers have adjusted their technologies to meet these TPPs. There is potential to adapt the TPP process beyond newborn care

Pengembangan Media “PAKOTA” (Papan Kosa Kata) Tema 2 Subtema 1 Materi Keragaman Benda Kelas 2 SD N Tanjungrejo 1

Abstrak. Dalam proses pembelajaran tidak semua materi dapat diajarkan melalui verbal saja. Seorang guru memerlukan alat berupa media pembelajaran untuk mempermudah penyampaian materi serta memudahkan siswa dalam memahami konsep materi yang diajarkan. Media pembelajaran yang digunakan dapat berupa cetak, audio, internet, ataupun berupa media yang berwujud (konkreat). Dengan adanya media pembelajaran, dapat meningkatkan semangat dan motivasi belajar siswa, dan tentunya kegiatan pembelajaran menjadi lebih menyenangkan dan tidak membosankan. Penelitian ini dilakukan untuk mengembangkan, menguji kevalidan, keterterapan, dan kemenarikan media pembelajaran “PAKOTA” (Papan Kosa Kata ) pada Tema 2 Subtema 1 kelas 2 SD N Tanjungrejo 1. Penelitian ini merupakan penelitian pengembangan (R&D) dengan model pengembangan ADDIE. Sebanyak 15 siswa kelas 2 SD N Tanjungrejo 1 menjadi sampel dalam penelitian ini. Penelitian ini menggunakan pendekatan kualitatif dan kuantitatif. Teknik pengumpulan data dilakukan dengan metode observasi, wawancara, angket dan dokumentasi. Instrumen pengumpulan data yang digunakan berupa angket validasi dan angket respon siswa. Hasil validitas media pembelajaran PAKOTA dinyatakan valid setelah dilakukan review oleh ahli media dan materi dengan presentase tingkat pencapaian sebesar 80% dengan kategori layak. Dilakukan uji coba lapangan  untuk mengetahui tingkat keterterapan dan kemenarikan media pembelajaran, dengan hasil presentase tingkat pencapaian sebesar 92% dengan kategori  sangat baik.Kata Kunci: Pengembangan, Media Pembelajaran, PAKOTA

Genocidio político, impunidad y crímenes contra la paz en Colombia (Sentencia)

En la 48ª sesión del Tribunal Permanente de los Pueblos del 25 al 27 de marzo de 2021 en Colombia se escucharon y evidenciaron el genocidio político, la impunidad y los crímenes contra la paz que el pueblo colombiano ha sufrido sistemáticamente, gracias a los valientes testimonios y luchas de los grupos campesinos, indígenas, estudiantiles, obreros, afrocolombianos, y de mujeres y hombres que se hicieron presentes en Medellín, Bucaramanga y Bogotá, donde sesionó el TPP. En este Tribunal, cuyo carácter es ético y de opinión, se condenó al Estado colombiano al encontrar evidencia de que existe una política estatal que, con la doctrina de destruir un «enemigo interno», ha venido exterminando a las comunidades, organizaciones y personas que ejercen una oposición al modelo que este representa. En este libro, publicado desde el Cinep/PPP con apoyo del TPP Colombia, se presenta la sentencia en su totalidad, con las acusaciones, marco referencial y condena al Estado colombiano y a quienes han sido sus aliados en esta política criminal que sigue en la impunidad. En las páginas que reúnen el fallo se documenta, además del horror y los atropellos a los cuales ha sido sometido el pensamiento crítico colombiano, la dignidad de personas y organizaciones que han resistido y dejan claro que, en Colombia, el pueblo se levanta por el pueblo.Prólogo. Pág. 6 Presentación del TPP. Pág. 10 Introducción. Pág. 13 Hechos. Pág. 23 Factores históricos y geopolíticos. Pág. 80 Aspectos esenciales del marco jurídico internacional y nacional. Pág. 99 Los Acuerdos de paz. Pág. 107 La calificación jurídica. Pág. 112 Fallo. Pág. 160 Recomendaciones. Pág. 167 Anexos documentales. Pág. 17